Obesity-update.com THE LATEST IN OBESITY RESEARCH AND WEIGHTLOSS DRUG DEVELOPMENT Join our list More information January 2005 VOLUME 7, ISSUE 1 Contents: Adipocytes Diet and exercise studies Drug development/drug studies Insulin resistance Leptin studies Miscellaneous Obesity and disease Obesity and genetics OTC supplements Tables of contents Adipocytes Phospholipid fatty acid composition altered in obese type 2 diabetic patients. January 4, 2005, (NewsRx.com & NewsRx.net) -- Obese type 2 diabetic patients and obese patients have comparable plasma phospholipid fatty acid compositions deviating from that of healthy individuals. "There exist controversial reports regarding the differences in phospholipid fatty acids in type 2 diabetic and obese patients as compared to controls. The study was aimed at assessing the combined effect of type 2 diabetes and obesity on the fatty acid composition of plasma phospholipids. The experimental group consisted of 23 Belgian obese type 2 diabetics on metformin. Two control groups were used: healthy lean and obese individuals in the same BMI range as the diabetics. Plasma phospholipids were isolated and their fatty acids and vinyl ether moieties were determined. Significance was set at p<0.01," investigators in Belgium report. "Plasma phospholipid fatty acids and plasmalogen-derived dimethyl acetals in diabetics deviated in many respects from these of lean controls but were not significantly different from those of obese non-diabetic patients," said Yanik Rodriguez and colleagues at Ghent University. "Therefore, the deviations of the fatty acid pattern of plasma phospholipids in type 2 diabetes may be attributed to obesity rather than to diabetes itself." (Press release) Obese type 2 diabetics and obese patients have comparable plasma phospholipid fatty acid compositions deviating from that of healthy individuals. Rodriguez Y, et al. (medline) Prostaglandins Leukot Essent Fatty Acids. 2004 Nov;71(5):303-8. ---- Insulin mimic found in fat. December 17, 2004 -- A newly discovered metabolic factor produced predominantly by visceral fat mimics the effects of insulin, according to a report published in this week's Science. The factor, called visfatin, lowered insulin levels in vivo and in vitro and activated the insulin receptor, although in a manner different from that of insulin. In recent decades, it has become apparent that adipose tissue is not a mere repository of triglycerides, but an extensive endocrine organ that secrets numerous adipocytokines -- hormones with key roles in regulating metabolism. "Visfatin should shed new light on the mechanism of insulin resistance and metabolic syndrome [a collection of disorders that includes high insulin and cholesterol levels, and excess body weight] and should help develop a new therapy," senior author Iichiro Shimomura of Osaka University told The Scientist in an email. Mitchell Lazar of the University of Pennsylvania, who was not involved in the study, was pleased with the "new player from adipose tissue." According to Lazar, adipocytokines can be split into two groups: "insulin resistance factors" (which decrease insulin action) include resistin, tumor necrosis factor alpha, and interleukin 6, while "insulin sensitivity factors" (which improve insulin action) include leptin, adiponectin, "and now visfatin -- which actually mimics insulin." (article) Visfatin: A protein secreted by visceral fat that mimics the effects of insulin. Fukuhara A, et al. (medline) Science. 2004 Dec 16; [Epub ahead of print]. Visfatin: A new adipokine. Hug C, et al. (medline) Science. 2004 Dec 16; [Epub ahead of print]. ---- Mest/Peg1 imprinted gene enlarges adipocytes and is a marker of adipocyte size. Takahashi M, et al. (medline) Am J Physiol Endocrinol Metab. 2005 Jan;288(1):E117-24. Epub 2005 Jan. Concomitant expression of adrenomedullin and its receptor components in rat adipose tissues. Fukai N, et al. (medline) Am J Physiol Endocrinol Metab. 2005 Jan;288(1):E56-62. Epub 2005 Jan. Adipocytes with increased hexosamine flux exhibit insulin resistance, increased glucose uptake, and increased synthesis and storage of lipid. McClain DA, et al. (medline) Am J Physiol Endocrinol Metab. 2004 Dec 21; [Epub ahead of print]. Postnatal diet-induced obesity in rats upregulates systemic and adipose tissue glucocorticoid metabolism during development and in adulthood: its relationship with the metabolic syndrome. Boullu-Ciocca S, et al. (medline) Diabetes. 2005 Jan;54(1):197-203. Relationships in women between body mass index and the intravascular metabolism of chylomicron-like emulsions. Oliveira MR, et al. (medline) Int J Obes Relat Metab Disord. 2004 Nov;28(11):1471-8. Resistin expression in 3T3-L1 adipocytes is reduced by arachidonic acid. Haugen F, et al. (medline) J Lipid Res. 2005 Jan;46(1):143-53. Epub 2004 Oct 16. Characterization of differentiated subcutaneous and visceral adipose tissue from children: the influences of TNF-{alpha} and IGF-I. Grohmann M, et al. (medline) J Lipid Res. 2005 Jan;46(1):93-103. Epub 2004 Oct 16. Adiposity signaling and biological defense against weight gain: absence of protection or central hormone resistance? Schwartz MW, et al. (medline) J Clin Endocrinol Metab. 2004 Dec;89(12):5889-97. Adiponectinemia in visceral obesity: impact on glucose tolerance and plasma lipoprotein-lipid levels in men. Cote M, et al. (medline) J Clin Endocrinol Metab. 2004 Dec 14; [Epub ahead of print]. Adipocyte regulation supplement Ectopic fat stores: housekeepers that can overspill into weapons of lean body mass destruction. Dulloo AG, et al. (medline) Int J Obes Relat Metab Disord. 2004 Dec;28 Suppl 4:S1-2. Concept of fat balance in human obesity revisited with particular reference to de novo lipogenesis. Schutz Y. (medline) Int J Obes Relat Metab Disord. 2004 Dec;28 Suppl 4:S3-S11. Failure of fat cell proliferation, mitochondrial function and fat oxidation results in ectopic fat storage, insulin resistance and type II diabetes mellitus. Heilbronn L, et al. (medline) Int J Obes Relat Metab Disord. 2004 Dec;28 Suppl 4:S12-21. Lipotoxicity, an imbalance between lipogenesis de novo and fatty acid oxidation. Lelliott C, et al. (medline) Int J Obes Relat Metab Disord. 2004 Dec;28 Suppl 4:S22-8.. Substrate cycling between de novo lipogenesis and lipid oxidation: a thermogenic mechanism against skeletal muscle lipotoxicity and glucolipotoxicity. Dulloo AG, et al. (medline) Int J Obes Relat Metab Disord. 2004 Dec;28 Suppl 4:S29-37. Role of energy charge and AMP-activated protein kinase in adipocytes in the control of body fat stores. Rossmeisl M, et al. (medline) Int J Obes Relat Metab Disord. 2004 Dec;28 Suppl 4:S38-44. Role of glucocorticoids in the physiopathology of excessive fat deposition and insulin resistance. Asensio C, et al. (medline) Int J Obes Relat Metab Disord. 2004 Dec;28(S4):S45-S52. Fat storage in pancreas and in insulin-sensitive tissues in pathogenesis of type 2 diabetes. Assimacopoulos-Jeannet F. (medline) Int J Obes Relat Metab Disord. 2004 Dec;28 Suppl 4:S53-7. Ectopic fat storage in heart, blood vessels and kidneys in the pathogenesis of cardiovascular diseases. Montani JP, et al. (medline) Int J Obes Relat Metab Disord. 2004 Dec;28 Suppl 4:S58-65. Lipotoxicity: the obese and endurance-trained paradox. Russell AP. (medline) Int J Obes Relat Metab Disord. 2004 Dec;28 Suppl 4:S66-71. Diet and exercise studies Physical inactivity for two days increases risk of serious illness. MU researcher find links to pre-diabetes, heart disease, obesity and hypertension. January 5, 2005, Columbia, MO -- In as little as two days of physical inactivity, a body's efficient use of insulin may decrease, according to two University of Missouri-Columbia researchers in a study published recently in the Journal of the Physiological Society. In a study involving rats, Frank Booth, professor of biomedical science and director of the MU Health Activity Center, and David Kump, a doctoral student in the Department of Medical Pharmacology and Physiology, found that insulin sensitivity decreases the longer the rats stay inactive. This decreased insulin efficiency may be a precursor to diabetes and other related diseases. "The less efficient your insulin is, the greater risk you have of diabetes, heart disease, obesity and hyptertension," Kump said. "Insulin works by taking glucose, or blood sugar, out of the blood stream and into the muscle to be used for energy. Our research found that when the rats stopped running for two days, the amount of sugar taken into the muscle in response to insulin was reduced by about one-third." (Press release) Alterations in insulin receptor signaling in the rat epitrochlearis muscle upon cessation of voluntary exercise. Kump DS, et al. (medline) J Physiol. 2004 Nov 18; [Epub ahead of print]. ---- Effects of high protein diets on thermogenesis, satiety and weight loss reviewed. January 3, 2004, (NewsRx.com & NewsRx.net) -- Scientists review the effects of high-protein diets on thermogenesis, satiety, and weight loss in a recent issue of the Journal of the American College of Nutrition. According to recent research from the United States, "For years, proponents of some fad diets have claimed that higher amounts of protein facilitate weight loss. Only in recent years have studies begun to examine the effects of high-protein diets on energy expenditure, subsequent energy intake, and weight loss as compared to lower protein diets. In this study, we conducted a systematic review of randomized investigations on the effects of high-protein diets on dietary thermogenesis, satiety, body weight, and fat loss." "There is convincing evidence that a higher protein intake increases thermogenesis and satiety compared to diets of lower protein content," said Thomas L. Halton and Frank B. Hu at Harvard University. "The weight of evidence also suggests that high protein meals lead to a reduced subsequent energy intake. Some evidence suggests that diets higher in protein result in an increased weight loss and fat loss as compared to diets lower in protein, but findings have not been consistent. In dietary practice, it may be beneficial to partially replace refined carbohydrate with protein sources that are low in saturated fat." "Although recent evidence supports potential benefit, rigorous longer-term studies are needed to investigate the effects of high-protein diets on weight loss and weight maintenance," concluded Halton and Hu. (Press release) The effects of high protein diets on thermogenesis, satiety and weight loss: a critical review. Halton TL, et al. (medline) J Am Coll Nutr. 2004 Oct;23(5):373-85. ---- Choosing the kind of fat to avoid obesity. January 3, 2005, (NewsRx.com & NewsRx.net) -- The type of fat ingested may create the conditions for or, on the other hand, prevent the development of obesity. This is the conclusion drawn by Patricia Perez Matute, PhD student at the department of physiology and nutrition at the University of Navarre, in her research which has received an international award from the medical journal, Clinical Science. The work was presented at the 6th Congress of the International Society for the Study of Fatty Acids and Lipids (ISSFAL, 2004) held in Brighton (Great Britain). The study forms part of the project entitled "Regulation of the expression and secretion of leptin and of other genes related to obesity through nutrients: the molecular mechanisms involved." The study, explained the author, arose from the observation that the ingestion of saturated fats appeared to lead to the development of obesity, while the polyunsaturated fatty acids, from fish oils, would appear to prevent and correct both obesity and insulin resistance. "In this sense, for example, Eskimos who ingest greater quantities of fish in their diet have lower rates of mortality from heart diseases frequently associated with obesity," she pointed out. This is why, the effect of eicosapentaenoic acid (EPA) - one of the omega-3 polyunsaturated fatty acids - on leptin, a gene involved in regulating body weight. "It was observed that EPA was capable of stimulating the secretion of leptin in primary cell cultures of fat from rats," explained Perez. This stimulating effect, in her view, is of great interest, "given that any strategy favoring the increase of leptin levels may well be beneficial for maintaining body weight during treatment for obesity and, thus, also obtain an improvement in those pathologies associated with obesity such as diabetes, atherosclerosis, etc." Moreover, the research provides information on the mechanisms involved in the regulation of the leptin gene, specifically in the role of glucose metabolism. The awarded research is entitled, "Increase in oxidation of glucose is involved in the stimulant effect of EPA on leptin secretion primary cultures of adipocites from the rat." (Press release) ---- Eating at fast-food restaurants more than twice per week is associated with more weight gain and insulin resistance in otherwise healthy young adults. December 30, 2004 -- Young adults who eat frequently at fast-food restaurants gain more weight and have a greater increase in insulin resistance in early middle age, according to a large multi-center study funded by the National Heart, Lung, and Blood Institute (NHLBI) and published in the January 1 issue of The Lancet*. After 15 years, those who ate at fast-food restaurants more than twice each week compared to less than once a week had gained an extra ten pounds and had a two-fold greater increase in insulin resistance, a risk factor for type 2 diabetes. Diabetes is a major risk factor for heart disease. "Obesity and diabetes are on the rise in this country and this important study highlights the value of healthy eating habits," said NHLBI Acting Director Barbara Alving, M.D. Fast-food consumption has increased in the United States over the past three decades. "It's extremely difficult to eat in a healthy way at a fast-food restaurant. Despite some of their recent healthful offerings, the menus still tend to include foods high in fat, sugar and calories and low in fiber and nutrients," said lead author Mark Pereira, Ph.D., assistant professor of epidemiology at the University of Minnesota. People need to evaluate how often they eat meals at fast-food restaurants and think about cutting back, according to Pereira. (Press release) Fast-food habits, weight gain, and insulin resistance (the CARDIA study): 15-year prospective analysis. Pereira MA, et al. Lancet. 2005 Jan 1;365(9453). Super-sized and diabetic by frequent fast-food consumption? Astrup A. Lancet. 2005 Jan 1;365(9453). ---- Study finds that both weight and exercise are key to longevity. December 22, 2004, Boston, MA -- New research findings from the Department of Nutrition at the Harvard School of Public Health and Brigham and Women's Hospital show that increased body fatness measured by body-mass index (BMI) and reduced physical activity are both strong and independent predictors of premature death in women. The study appears in the December 23, 2004 issue of the New England Journal of Medicine. Body-mass index is determined by dividing an individuals' weight in kilograms by the square of height in meters. For non-metric, weight in pounds is divided by the square of height in inches, then multiplied by 703. A BMI over 25 is considered overweight. Approximately two thirds of Americans are classified as overweight or obese. More than 115,000 participants who were free of cardiovascular disease or cancer, between the ages of 30 and 55 and had filled out biennial health and lifestyle questionnaires between 1976 and 2000 were chosen for the study from the Brigham and Women's Hospital-based Nurses' Health Study. In the questionnaires the women were asked to report on average how much time was spent per week on moderate physical activities such as brisk walking, and vigorous physical activities, among them, jogging, running, bicycling, playing tennis and swimming laps. Women who spent 3.5 hours per week or more exercising were considered physically active. (Press release) Adiposity as compared with physical activity in predicting mortality among women. Hu FB, et al. (medline) N Engl J Med. 2004 Dec 23;351(26):2694-703. See also: Study: Active but obese face greater risks. Associated Press press release, December 23, 2004. Physical activity, relative body weight, and risk of death among women. Jacobs DR Jr, et al. (medline) N Engl J Med. 2004 Dec 23;351(26):2753-5. Associations of fitness and fatness with mortality in Russian and American men in the lipids research clinics study. Stevens J, et al. (medline) Int J Obes Relat Metab Disord. 2004 Nov;28(11):1463-70. ---- Exercise before fatty meal may curb bad effects. December 20, 2004, New York (Reuters Health) -- People gearing up for an indulgent holiday feast may want to make time for some pre-meal exercise. A small study out Monday suggests that a long walk before a fatty meal can lessen the effects of high fat intake on blood vessel function. Eating high-fat foods is known to transiently elevate levels of blood fats such as triglycerides, and recent research has shown that a rich meal can also temporarily impair the functioning of the lining of blood vessels-called the endothelium. The new study, published in the December 21st issue of the Journal of the American College of Cardiology, suggests that moderate exercise can blunt these effects in both thin and obese middle-aged men. The 20 men in the study ate a rich meal -- featuring whipped cream, chocolate and a whopping 80 grams of fat -- under two conditions on separate days. In one condition, the men spent 90 minutes walking on a treadmill the day before the meal; in the other, they had their meal after an exercise-free day. (Press release) Effects of prior moderate exercise on postprandial metabolism and vascular function in lean and centrally obese men. Gill JM, et al. (medline) J Am Coll Cardiol. 2004 Dec 21;44(12):2375-82. ---- Yo-yo diet redistributes hexachlorobenzene in body tissue. Olestra+caloric cut boosts toxic excretion; the dioxin link. December 17, 2004, Bethesda, MD -- Perhaps Ukrainian opposition leader Viktor Yushchenko should try an "Olestra diet" to rid his body of dioxin. It wouldn't be the first time that the "fake fat" product was used as an emergency agent to flush out dioxin, one of a group of chlorinated hydrocarbons that are toxic, lipophilic (attracted to fat) -- and persistent in the environment and animal tissues. About five years ago, two Austrian women suffering from dioxin poisoning were given olestra snacks, which resulted in removal of dioxin at 10 times the normal rate, according to some reports. In an as-yet-unpublished study, researchers at the University of Cincinnati School of Medicine, along with Trevor Redgrave at the University of Western Australia, treated a patient with PCB toxicity over a two-year period with olestra in the form of fat-free Pringles. The patient's chloracne disappeared and the PCB level in fat tissue dropped dramatically. The same University of Cincinnati School of Medicine team is reporting new research that sheds light into how diet affects retention and re-distribution through the weight gain-loss-regain cycle of chlorinated hydrocarbons, which include DDT, PCBs and dioxins. They also looked at the effects of the additive olestra, which is made by Procter & Gamble, on this redistribution and perhaps more importantly, on excretion of toxins from the body. (Press release) Effects of yo-yo diet, caloric restriction, and olestra on tissue distribution of hexachlorobenzene. Jandacek RJ, et al. (medline) Am J Physiol Gastrointest Liver Physiol. 2004 Oct 28; [Epub ahead of print]. ---- Effects of weight loss and physical activity on skeletal muscle mitochondrial function in obesity. Menshikova EV, et al. (medline) Am J Physiol Endocrinol Metab. 2004 Dec 7; [Epub ahead of print]. Decrease of plasma apolipoprotein A-IV during weight reduction in obese adolescents on a low fat diet. Lingenhel A, et al. (medline) Int J Obes Relat Metab Disord. 2004 Nov;28(11):1509-13. Effects of moderate consumption of white wine on weight loss in overweight and obese subjects. Flechtner-Mors M, et al. (medline) Int J Obes Relat Metab Disord. 2004 Nov;28(11):1420-6. Drug development/drug studies Sankyo and Metabasis announce initiation of phase IIb study for diabetes drug, CS-917. January 5, 2005, Tokyo, Japan and San Diego, CA -- Sankyo Co., Ltd. and Metabasis Therapeutics, Inc. today announced the recent initiation of a Phase IIb clinical trial of CS-917 in patients with type 2 diabetes. Sankyo licensed CS-917 from Metabasis and is responsible for the global development of the compound. The randomized, placebo controlled, double blind Phase IIb study is designed to evaluate the effectiveness of CS-917 in lowering blood glucose levels in patients with type 2 diabetes. Efficacy of CS-917 will be evaluated by measuring levels of hemogloblin A1c (HbA1c), an accurate long-term index of a patient's average blood glucose control. Results of the Phase IIb study will be used to select the appropriate dosage of CS-917 for use in Phase III clinical trials. "With the number of diabetes cases rising worldwide, it has never been more important to find new ways to help patients control their blood glucose levels," said Tomas Bocanegra, M.D., Vice President of Clinical Development at Sankyo's U.S. subsidiary, Sankyo Pharma Inc. "We hope to provide a new, important treatment option for the millions of patients affected by type 2 diabetes." CS-917, the first in a new class of investigational drugs called fructose 1-6 bisphosphatase inhibitors (FBPase), appears to inhibit a metabolic pathway in the liver called gluconeogenesis, which is responsible for the excessive production of glucose by patients with type 2 diabetes. (Press release) ---- Bristol-Myers Squibb provides regulatory update for Muraglitazar and Abatacept. December 23, 2004, Princeton, NJ -- Bristol-Myers Squibb Company (NYSE: BMY) today announced that the company submitted a New Drug Application to the U.S. Food and Drug Administration (FDA) for muraglitazar, an investigational agent under development for the treatment of patients with type 2 diabetes. Bristol-Myers Squibb and Merck & Co., Inc. are collaborators in the global development and commercialization of muraglitazar. Muraglitazar, discovered by Bristol-Myers Squibb, has the potential to be the first in a novel class of drugs known as dual peroxisome proliferator activated receptor (PPAR) agonists to be approved for marketing in the U.S. (Press release) See also: BMS submits muraglitazar in the USA. Marketletter via NewsEdge Corporation press release, January 5, 2005. ---- Arena Pharmaceuticals initiates phase 2 efficacy study for its novel anti-obesity compound. December 22, 2004, San Diego /PRNewswire-FirstCall/ -- Arena Pharmaceuticals, Inc. (Nasdaq: ARNA) announced today that it has started dosing patients in a Phase 2 clinical trial of APD356, an orally administered small molecule designed to regulate satiety for the treatment of obesity. This compound is a selective agonist of 5-HT2C serotonin receptors, which are concentrated in the hypothalamus, an area of the brain known to play an important role in regulating food intake and metabolism. This Phase 2 clinical trial of APD356 is a randomized, double-blinded, multiple-dose, 28-day trial examining 400 obese volunteers. Arena expects that the trial will compare doses of 1, 5 and 15 mg of APD356 to a placebo and will evaluate weight loss after administration once daily for 28 days. Doses for the Phase 2 trial were chosen to bracket the 10 mg dose that evidenced a pharmacologic signal (a reduction in meal size) with a single dose in Arena's Phase 1a trial. The 1 mg dose was chosen as the lowest dose because Arena believes that a 1 mg dose has the potential to produce therapeutic drug levels in the central nervous system if APD356, as observed in rats, achieves higher concentrations in the human brain than in blood. Arena expects to announce initial results from this trial in the second quarter of 2005. "The initiation of this Phase 2 trial of our lead anti-obesity compound marks a significant achievement for Arena," stated Jack Lief, Arena's President and CEO. "This strengthens our pipeline of compounds, which have the potential to treat major unmet medical needs. We anticipate that this Phase 2 study will provide further favorable safety data and validate the preliminary efficacy data observed in earlier pre-clinical studies of APD356." (Press release) ---- Manhattan Pharmaceuticals, Inc. receives SwissMedic's approval for initiation of human safety trials for oleoyl estrone. December 20, 2004, New York NY -- The Swiss governmental medical regulatory authority, SwissMedic, issued its formal approval for Manhattan Pharmaceuticals, Inc. ("Manhattan" OTCBB: MHTT) to initiate human safety trials for Oleoyl estrone (OE). Oleoyl estrone is Manhattan's lead product candidate, and under development as an obesity therapeutic. "Obtaining SwissMedic's regulatory approval to initiate human trials is an important milestone for Manhattan", said Dr. Leonard Firestone, Manhattan's Chief Executive Officer and President. "Our scientific team has worked diligently to design several highly efficient trials to assess the safety and tolerability, in obese volunteers, of this naturally-occurring molecule. We are very pleased that we may now proceed toward the patient enrollment process." In November 2003, the Manhattan announced the first, peer reviewed publication reporting human physiologic responses to OE, including marked weight loss, during 27 months of oral administration. More recently the Company reported favorable preclinical toxicology and safety data for OE at the 13th Annual Meeting of the European Congress on Obesity in May 2004. (Press release) ---- Takeda announces to place its anti-diabetic agent TAK-559 on clinical hold. December, 20, 2004, Osaka, Japan -- Takeda Pharmaceutical Company Limited ("Takeda") announced today that its investigational compound TAK-559, an anti-diabetic agent by improving insulin resistance, is placed on clinical hold because of findings of abnormalities in liver enzyme tests in a small number of patients during the course of the phase III studies. As a result, Takeda judged it necessary to reevaluate the product's safety profile. TAK-559 is under development as an insulin resistance improving agent, and is in the phase I clinical stage and phase III in Japan and the US/Europe respectively. The phase III clinical studies have been conducted since 2003 with more than 1,000 patients mainly in the US. We will conduct thorough analysis of the data obtained during the course of phase III studies to date in order to decide the future development plan of this product. (Press release) ---- Epilepsy drug useful for binge-eating disorder. December 16, 2004, New York (Reuters Health) - The results of a small study published in the Journal of Clinical Psychiatry suggest that the epilepsy drug topiramate may provide long-term benefits for people with binge-eating disorder and obesity. Dr. Susan L. McElroy, of the University of Cincinnati College of Medicine, Ohio, and colleagues studied 61 such subjects, who were randomly selected to take topiramate or an inactive "placebo." A total of 44 patients received at least one dose of topiramate, according to the report, and results were available for 43 who reached the final dose of 250 milligrams daily. All 43 participants not only experienced a significant decline in the number of weekly binge episodes, but also saw a significant reduction in body weight. Further studies of "topiramate in the long-term treatment of binge-eating disorder appear warranted," the research team concludes. Topiramate in the long-term treatment of binge-eating disorder associated with obesity. McElroy SL, et al. (medline) J Clin Psychiatry. 2004 Nov;65(11):1463-9. See also: A randomized double-blind placebo-controlled study of the long-term efficacy and safety of topiramate in the treatment of obese subjects. Wilding J, et al. (medline) Int J Obes Relat Metab Disord. 2004 Nov;28(11):1399-410. ---- ConjuChem reports positive efficacy and tolerability results in phase II clinical trial. DAC™:GLP-1 hits primary endpoint in type 2 diabetes trial. December 15, 2004, Montreal, CA -- ConjuChem Inc. (TSX:CJC) today announced the main results from its Phase II clinical trial that is evaluating the Company's proprietary compound DAC™:GLP-1 to treat Type 2 Diabetes in combination with Metformin. The study demonstrated that DAC™:GLP-1 significantly reduced blood glucose levels in patients who were on oral anti-diabetic medications, however not in glycemic control. The Company also announced today initial positive results from an ongoing Phase I program evaluating new diluents for DAC™:GLP-1 which are being developed to further enhance the drug's tolerability profile and dosing convenience. "Today's results confirm that DAC™:GLP-1 is both highly effective, even at low dose levels, and tolerable - re-establishing this compound's potential to become a best-in-class product," said Dr. Jean Paul Castaigne, Chief Operating Officer of ConjuChem. "As well, there has been encouraging progress in the new diluent study, with a marked improvement in tolerability which holds the promise for an even more convenient dosing regimen." (Press release) See also: ConjuChem successfully completes phase I multi-dose trial for DAC™:GRF. ConjuChem press release, December 9, 2004. ---- Biovitrum AB and Discovery Partners International, Inc. form research alliance. December 14, 2004, Stockholm, Sweden, and San Diego, /PRNewswire-FirstCall via COMTEX/ -- Biovitrum AB and Discovery Partners International, Inc. (Nasdaq: DPII) today announced that they have entered into a drug discovery and development alliance. Biovitrum and Discovery Partners will work together to identify small molecule lead compounds suitable for advancing targets within the metabolic disease area. Under the terms of this agreement, Biovitrum will get access to DPI's comprehensive compound collection and its proprietary process and data management tools. Financial terms of the collaboration were not disclosed. "We are impressed by DPI's integrated drug discovery approach and expect that this will add significant value to our ongoing lead discovery programs," said Mats Pettersson, Chief Executive Officer of Biovitrum. (Press release) ---- Successful trial results for world-first obesity drug. December 13, 2004, Melbourne Australia -- An Australian-owned obesity drug, developed by Melbourne-based biotechnology company Metabolic Pharmaceuticals Limited, is set to enter final human trials next year after successfully completing a Phase 2b human trial which proved that the drug induces weight loss and is very well tolerated with no evidence of the side effects commonly experienced with existing obesity drugs. The drug, which stimulates the metabolism of body fat, is the first of its kind in the world. All other obesity drugs artificially reduce appetite or food absorption. The drug -- codenamed AOD9604 -- was taken orally once daily by 300 obese patients at five trial sites over a 12-week period. Six doses were used -- 0 mg (placebo), 1 mg, 5 mg, 10 mg, 20 mg and 30 mg. The group receiving the 1 mg dose lost the most weight, averaging a weight loss over the 12 weeks of 2.8 kilograms, more than triple the weight lost by those on placebo, who lost an average of 0.8 kilograms. The rate of weight loss was maintained throughout the treatment period, an encouraging trend for expectations of longer-term dosing. The weight lost by the 1 mg group was slightly more than that achieved by the world's largest selling prescription obesity medication in similar trials over the same period, without its troublesome side effects. The trial results also demonstrated a small but consistent improvement in cholesterol profiles, and a reduction in the number of patients with impaired glucose tolerance. (Press release) ---- Changes in body weight and serum lipid profile in obese patients treated with orlistat in addition to a hypocaloric diet: a systematic review of randomized clinical trials. Hutton B, et al. (medline) Am J Clin Nutr. 2004 Dec;80(6):1461-8. Growth hormone treatment reduces abdominal visceral fat in postmenopausal women with abdominal obesity: a 12-month placebo-controlled trial. Franco C, et al. (medline) J Clin Endocrinol Metab. 2004 Dec 14; [Epub ahead of print]. Central structures necessary and sufficient for ingestive and glycemic responses to Urocortin I administration. Daniels D, et al. (medline) J Neurosci. 2004 Dec 15;24(50):11457-62. Insulin resistance Metabolically obese but normal-weight women characterized. January 4, 2005 (NewsRx.com & NewsRx.net) -- Metabolically obese but normal-weight women possess characteristic metabolic and behavioral features. "A unique subset of individuals termed metabolically obese but normal weight (MONW) has been identified. These young women are potentially at increased risk for development of the metabolic syndrome despite their young age and normal body mass index. We seek to determine metabolic and behavioral factors that could potentially distinguish MONW women from young women with a normal metabolic profile. Ninety-six women were classified as MONW (n=12) or non-MONW (n=84) based on a cut point of insulin sensitivity (as estimated by the homeostasis model assessment)," scientists in Canada and the United States report. "Potentially distinguishing phenotypes between groups measured included serum lipids, ghrelin, leptin, adiponectin, body composition and body fat distribution, resting and physical activity energy expenditure, peak oxygen uptake, dietary intake, dietary behavior, and family history and lifestyle variables," stated Florence Conus at the University of Montreal in Canada and collaborators in Canada and the U.S. "Despite a similar body mass index between groups, MONW women showed higher percent body fat, lower fat-free mass, lower physical activity energy expenditure, and lower peak oxygen uptake than non-MONW women." "Plasma cholesterol level was higher in MONW women, whereas no differences were noted for other blood lipids, ghrelin, leptin, adiponectin, and resting energy expenditure," reported the investigators. "MONW women had lower dietary restraint scores than non-MONW women, but no differences were noted in disinhibition, hunger, and dietary intake. Stepwise regression analysis performed on all subjects showed that 33.5% of the unique variance of the homeostasis model assessment was explained with the variables of percentage of body fat (17.1%), level of dietary restraint (10.4%), and age (6%)." The researchers concluded, "Both metabolic and dietary behavioral variables contribute to the deleterious metabolic profile of MONW women. They display lower insulin sensitivity due potentially to a cluster of sedentary behavior patterns that contribute to their higher adiposity. Furthermore, cognitive attitudes toward food (i.e., dietary restraint) and concomitant lifestyle behaviors may play a role in regulating insulin sensitivity in metabolically obese but normal weight women." (Press release) Metabolic and behavioral characteristics of metabolically obese but normal-weight women. Conus F, et al. (medline) J Clin Endocrinol Metab. 2004 Oct;89(10):5013-20. ---- IL-6 gene polymorphisms associated with type 2 diabetes. December 31, 2004, (NewsRx.com & NewsRx.net) -- The interleukin-6 gene polymorphisms C-174G and A-598G are associated with type 2 diabetes. "Elevated blood concentrations of IL-6 have been shown to predict type 2 diabetes. Because the impact of IL-6 gene polymorphisms on diabetes status, parameters of the metabolic syndrome, and low-grade systemic inflammation has not been analyzed in a population-based study, we investigated the association of the IL-6 single nucleotide polymorphisms C-174G and A-598G on these parameters in 704 elderly participants of the Cooperative Research in the Region of Augsburg (KORA) Survey 2000. Both -174G and -598G alleles were significantly associated with type 2 diabetes (-174G: odds ratio=1.51, 95% CI=1.11 -2.07, p=0.0096; -598G: odds ratio=1.56, 95% CI=1.13-2.15, p=0.0069) but not with impaired glucose tolerance," scientists in Germany report. "In subgroup analyses, the association reached statistical significance in men and in leaner subjects (body mass index less than or equal to28.7 kg/m2, i.e., study median) but not in women or more obese persons," stated Thomas Illig at the GSF National Research Center for Environment and Health in Neuherberg and collaborators in Germany. "Circulating IL-6 levels were not associated with the IL-6 polymorphisms, but significantly elevated levels of the chemokine monocyte chemoattractant protein-1/CC chemokine ligand 2 in carriers of the protective genotypes indicated an indirect effect of these single nucleotide polymorphisms on the innate immune system." (Press release) Significant association of the interleukin-6 gene polymorphisms C-174G and A-598G with type 2 diabetes. Illig T, et al. (medline) J Clin Endocrinol Metab. 2004 Oct;89(10):5053-8. ---- IRS2 takes center stage in development of type 2 diabetes. December 31, 2004, (NewsRx.com & NewsRx.net) -- According to recent research published in the Journal of Clinical Investigation, "The etiology of type 2 diabetes is characterized by obesity, insulin and leptin resistance, and compensatory beta-cell hyperplasia followed by islet degeneration, resulting in the eventual dysregulation of glucose and lipid homeostasis." "The recent identification of insulin receptor substrate 2 (IRS2) as a central player in the pathophysiology of many of these processes suggests a potentially unifying molecular link underlying the initiation and progression of type 2 diabetes," wrote Matthew J. Brady at the University of Chicago. (Press release). IRS2 takes center stage in the development of type 2 diabetes. Brady MJ. (medline) (article) J Clin Invest. 2004 Oct;114(7):886-8. Comment on: Dysregulation of insulin receptor substrate 2 in beta cells and brain causes obesity and diabetes. Lin X, et al. (medline) (article) J Clin Invest. 2004 Oct;114(7):908-16. ---- Oxidants link obesity to diabetes. December 20, 2004 -- Individuals with the metabolic syndrome are at risk of coronary heart disease, stroke, vascular disease, and type 2 diabetes. Although risk factors for this syndrome are known to include obesity, physical inactivity, and genetic factors, the mechanistic role of obesity is not completely understood. In the December 15 issue of the Journal of Clinical Investigation, Iichiro Shimomura and researchers from Osaka University, Japan, show that fat cells of obese mice produce increased levels of toxic oxygen molecules known as reactive oxygen species (ROS) as well as the enzyme NADPH oxidase. Furthermore, these cells express decreased levels of antioxidative enzymes that are responsible for destroying these toxic forms of oxygen. The effect of this oxidative stress causes changes in the production of fat-derived hormones known as adipocytokines. The authors found that treatment of these mice with apocynin -- an antioxidant that inhibits NADPH oxidase -- reduced ROS production in fat cells, restored adipocytokine production to normal, improved diabetes, and reduced the levels of fat present in the blood and liver. The results suggest that accumulated fatty tissue is a major source of ROS in obesity and acts as an early trigger of the metabolic syndrome. While it is too early to suggest that taking antioxidants may counter the development of obesity-associated metabolic syndrome, the steps leading to excess ROS generation may represent a potentially useful therapeutic target. Increased oxidative stress in obesity and its impact on metabolic syndrome. Furukawa S, et al. (medline) (article) J Clin Invest. 2004 Dec;114(12):1752-61. Oxidants link obesity to diabetes. (article) J Clin Invest. 2004 Dec;114(12):1689. See also: New obesity study implies antioxidant power. NutraIngredients.com press release, December 16, 2004. ---- Depression ups diabetes risk in middle-aged women. December 17, 2004, New York (Reuters Health) - Results of a new study provide more evidence that being depressed increases the likelihood of developing diabetes. People, as well as their doctors, "should recognize that depressive symptoms can increase risk of diabetes and are related to higher levels of insulin resistance, which is a risk factor for diabetes," investigators write in the medical journal Diabetes Care. "Patients should be encouraged to seek treatment for clinically significant depressive symptoms and to maintain or adopt active lifestyles, healthy diets, and weight loss if needed to reduce the risk of diabetes," they add. Dr. Susan A. Everson-Rose, from Rush University Medical Center in Chicago, and associates analyzed data on depression and risk of diabetes in 2,662 women enrolled in a study of health and aging. (Press release) Depressive symptoms, insulin resistance, and risk of diabetes in women at midlife. Everson-Rose SA, et al. (medline) Diabetes Care. 2004 Dec;27(12):2856-62. ---- Early changes in insulin secretion and action induced by high-fat diet are related to a decreased sympathetic tone. Cruciani-Guglielmacci C, et al. (medline) Am J Physiol Endocrinol Metab. 2005 Jan;288(1):E148-54. Epub 2005 Jan. Deficiency of subsarcolemmal mitochondria in obesity and type 2 diabetes. Ritov VB, et al. (medline) Diabetes. 2005 Jan;54(1):8-14. Miscellaneous Irregular patterns in daily weight chart at night predict weight regain. January 4, 2005, (NewsRx.com & NewsRx.net) -- According to a study from Japan, "This study examined whether charting daily weight patterns can predict weight regain in obese patients. The subjects were 98 moderately obese Japanese women aged 23 to 66 years who were obliged to precisely record their daily weights during the initial 4-month education period, but not thereafter. The patients were followed up at 8, 12, and 16 months. Abdominal fat areas and blood samples were assessed in the outpatient clinic at 0, 4, and 16 months." "The standard deviations (SDs) of the differences in body weight between 'after waking up' and 'after breakfast' (SDa), 'after dinner' (SDb), and 'before going to bed' (SDc) were calculated, which were parameters reflecting the fluctuations in the daily weight patterns during the first four months," said Misuzu Tanaka at Nakamura-Gakuen University and collaborators in Japan. "SDc, but not SDa or SDb, was correlated positively with weight regain at 8, 12, and 16 months (p=0.049, p=0.002, and p=0.001, respectively)." "There were significant differences in temporal change in body weight and abdominal visceral fat between the small SDc group (SDcless than or equal to25th percentile) and the large SDc group (SDc>75th percentile), but not for subcutaneous abdominal fat or the serum concentrations of glucose, insulin, or lipids," reported the researchers. "The results indicate that fluctuation of body weight immediately before going to bed is useful for predicting the rebound in body weight." (Press release) Irregular patterns in the daily weight chart at night predict body weight regain. Tanaka M, et al. (medline) Exp Biol Med (Maywood). 2004 Oct;229(9):940-5. ---- Metabolic profile of hippocampus of Zucker diabetic fatty rats assessed. December 31, 2004, (NewsRx.com & NewsRx.net) -- Scientists have used in vivo 1H magnetic resonance spectroscopy to assess a metabolic profile of the hippocampus of Zucker diabetic fatty rats. According to recent research from the Netherlands, "Localized in vivo 1H magnetic resonance spectroscopy (MRS) was used to investigate metabolite levels in the brain of adult Zucker diabetic fatty (ZDF) rats, an animal model for type 2 diabetes mellitus. This study focused on the hippocampus, assumed to be one of the main brain areas affected by this disease. Together with an almost five-fold increase in blood glucose concentration measured by glucose oxidation, significant increases were found in the hippocampal concentrations of glucose (4.93 vs 1.66 mM p<0.001), myo-inositol (6.52 vs 4.30 mM; p<0.05), and total creatine (12.71 vs 10.50 mM; p<0.05) in ZDF rats (n=5) compared with littermates (n=5)." "Although no obvious alterations were detected in the hippocampal levels of other metabolites, including NAA+NAAG and choline-containing compounds in the ZDF rats, the increase in Glc and Ins levels is in line with elevated brain tissue contents of these metabolites in patients with diabetes mellitus," stated Marinette van der Graaf and colleagues at the University of Nijmegen. van der Graaf and associates published their study in NMR in Biomedicine (Metabolic profile of the hippocampus of Zucker diabetic fatty rats assessed by in vivo H-1 magnetic resonance spectroscopy. NMR Biomed, 2004;17(6):405-410). (Press release) Metabolic profile of the hippocampus of Zucker diabetic fatty rats assessed by in vivo 1H magnetic resonance spectroscopy. van der Graaf M, et al. (medline) NMR Biomed. 2004 Oct;17(6):405-10. ---- American living makes you fat. December 22, 2004 -- Being in America makes you fat, according to a study published recently in the Journal of the American Medical Association. Researchers from various medical establishements across the States noted that while the prevalence of obesity has increased substantially in the US since the 1980s, little is known about the obesity rate within this subsection of society. Immigrants, moreover, are the fastest growing segment of the US population. Led by Mita Sanghavi Goel, the scientists set out to estimate the prevalence of obesity among immigrants, looking at how long people had been in the States, their diet, exercise regime and country of origin. The researchers found that the prevalence of obesity was 16 percent among immigrants and 22 percent among US-born individuals. However, there was a significant increase in the likelihood of an individual being obese if he/she had lived in the US for more than 15 years. "The age- and sex-adjusted prevalence of obesity was 8 percent among immigrants living in the United States for less than one year, but 19 percent among those living in the United States for at least 15 years," said the scientists (JAMA 2004;292:2860-2867). (Press release) Obesity among US immigrant subgroups by duration of residence. Goel MS, et al. (medline) JAMA. 2004 Dec 15;292(23):2860-7. ---- Does the lack of sleep make you fat? December 7, 2004 -- The recent rise in obesity may be partly due to the reduced amount of time we spend asleep, according to new research from the University of Bristol, UK. Dr Shahrad Taheri from Bristol University, and colleagues in the United States, examined the role of two key hormones that are involved in regulating appetite -- ghrelin and leptin. Ghrelin increases feelings of hunger while leptin acts to suppress appetite. People who habitually slept for 5 hours were found to have 15% more ghrelin than those who slept for 8 hours. They were also found to have 15% less leptin. These hormonal changes may cause increased feelings of hunger, leading to a foraging in the fridge for food. Dr Taheri, lead author of the study, said: "We found that people who slept for shorter durations have reduced leptin and elevated ghrelin. These differences are likely to increase appetite and, in societies where food is readily available, this may contribute to obesity. Individuals who spent less than 8 hours sleeping were shown to have a greater likelihood of being heavier. Good sleep, in combination with other lifestyle modifications may be important in fighting obesity". (Press release) See also: Stanford study links obesity to hormonal changes from lack of sleep. Press release, December 6, 2004. Why lost sleep equals gained weight. Daily Times article, December 6, 2004. Short sleep duration is associated with reduced leptin, elevated ghrelin, and increased body mass index. Taheri S, et al. (medline) (article) PLoS Med. 2004 Dec;1(3):e62. Epub 2004 Dec 7. Brief communication: Sleep curtailment in healthy young men is associated with decreased leptin levels, elevated ghrelin levels, and increased hunger and appetite. Spiegel K, et al. (medline) Ann Intern Med. 2004 Dec 7;141(11):846-50. Summaries for patients. Sleep duration and levels of hormones that influence hunger. (medline) (article) Ann Intern Med. 2004 Dec 7;141(11):I52. A good night's sleep: future antidote to the obesity epidemic? Flier JS, et al. (medline) Ann Intern Med. 2004 Dec 7;141(11):885-6. ---- Acquired obesity is associated with increased liver fat, intra-abdominal fat, and insulin resistance in young adult monozygotic twins. Pietilainen KH, et al. (medline) Am J Physiol Endocrinol Metab. 2004 Dec 7; [Epub ahead of print]. Obesity and disease Obesity-related leptin regulates Alzheimer's Abeta. Fewlass DC, et al. (medline) FASEB J. 2004 Dec;18(15):1870-8. Obesity-associated hypertension: new insights into mechanisms. Rahmouni K, et al. (medline) Hypertension. 2005 Jan;45(1):9-14. Epub 2004 Dec 06. Weight loss and the renin-angiotensin-aldosterone system. Engeli S, et al. (medline) Hypertension. 2005 Jan 3; [Epub ahead of print]. Obesity and genetics Hypothalamic melanin-concentrating hormone increased in obesity. January 4, 2005, (NewsRx.com & NewsRx.net) -- Dietary-obese rats have increased hypothalamic melanin-concentrating hormone and MCH receptor levels. "Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide that stimulates feeding and increases body weight in rodents. We studied the role of the system in energy homeostasis and its regulation by the satiety signals, leptin and insulin. We used real-time PCR to measure the hypothalamic expression of MCH and its receptor (MCHR1) in two contrasting models of altered nutritional status, namely, obesity induced by 8 weeks' voluntary overeating and food restriction for 10 days," researchers in England report. "Diet-fed rats were stratified according to final total fat-pad mass into a 'high fat gain' group (HG) and 'low fat gain' group (LG)," said Joanne C. Elliott and collaborators at Liverpool University and AstraZeneca R&D. "MCH mRNA levels were increased by 31% (p>0.05) and 49% (p<0.05) in the LG and HG, respectively, compared with controls. MCHR1 mRNA levels rose by 118% in the LG (p<0.01) and 85% in the HG (p<0.01). There were significant positive correlations (p<0.05) between plasma leptin concentration and both MCH and MCHR1 mRNA levels, and between plasma insulin and MCHR1 expression. A positive correlation was also observed between MCH and MCHR1 mRNA levels (p<0.05)." "Food-restricted rats showed no significant alterations in the levels of either MCH mRNA or MCHR1 mRNA," stated Elliott and her coauthors. "In a second experiment, we measured MCH peptide levels in five discrete hypothalamic areas of dietary-obese rats. MCH concentrations were significantly increased in the arcuate nuclei of the HG (p<0.05) and the paraventricular nuclei of both the LG (p<0.05) and HG (p<0.05), compared with their lean counterparts. These results suggest that the MCH system becomes more active in dietary obesity and could be involved in enhancing appetite for palatable food." The investigators concluded, "The possibility that MCH and MCHR1 expression are positively regulated by leptin and insulin, which normally inhibit feeding, is a putative explanation for how appetite for palatable food is able to override mechanisms that prevent the development of obesity." (Press release) Increases in melanin-concentrating hormone and MCH receptor levels in the hypothalamus of dietary-obese rats. Elliott JC, et al. (medline) Brain Res Mol Brain Res. 2004 Sep 28;128(2):150-9. ---- Alcoholism and excessive food intake may share chemical pathways in the brain. December 31, 2004 -- Galanin is one of several neuropeptides known to increase food intake. Previous findings have suggested that galanin may also be involved in alcohol consumption and/or the motivation to drink alcohol beverages. Most recently, researchers have discovered that giving galanin microinjections to rodents can increase their voluntary alcohol intake. Their findings are published in the December issue of Alcoholism: Clinical & Experimental Research. "Galanin's well-known effects of increasing food intake, especially the intake of fat-rich diets, was one of the early reasons we investigated it," said Michael J. Lewis, a senior fellow working with Dr. Bart Hoebel in his laboratory in the Department of Psychology at Princeton University and Sarah Leibowitz at Rockefeller University, and corresponding author for the study. "Alcohol is the only drug of abuse that can also qualify as a calorie-rich food, and it undoubtedly has important interactions with systems that control food intake and nutrition." Lewis added that alcohol, galanin and food intake have another area of commonality: all are stimulants of the neurotransmitter dopamine, which has been linked by numerous studies to the rewarding effects and "high" produced by potent drugs of abuse such as nicotine, cocaine and heroin. "While many brain neurochemicals have been examined for their role in modulating neurobiological responses to alcohol, the role of neuropeptide pathways, particularly those that have been shown to be involved with feeding and body weight regulation, have largely been ignored," added Todd E. Thiele, associate professor in the department of psychology at the University of North Carolina at Chapel Hill. "Recent research has implicated a number of peptides and proteins known to control food intake in alcohol consumption, including neuropeptide Y, cholecystokinin, the melanocortins, and leptin. This paper is one of the first demonstrations of an important role for galanin in modulating alcohol intake, and at the same time adds to the growing list of peptides that may have overlapping control of both alcohol and food ingestion." (Press release) Galanin microinjection in the third ventricle increases voluntary ethanol intake. Lewis MJ, et al. (medline) Alcohol Clin Exp Res. 2004 Dec;28(12):1822-8. ---- Bombesin and nutrients independently and additively regulate hormone release from GIP/Ins cells. Li L, et al. (medline) Am J Physiol Endocrinol Metab. 2005 Jan;288(1):E208-15. Epub 2005 Jan. Neuromedin beta: a strong candidate gene linking eating behaviors and susceptibility to obesity. Bouchard L, et al. (medline) Am J Clin Nutr. 2004 Dec;80(6):1478-86. Genetic linkage and association of the growth hormone secretagogue receptor (ghrelin receptor) gene in human obesity. Baessler A, et al. (medline) Diabetes. 2005 Jan;54(1):259-67. Growth hormone overexpression in the central nervous system results in hyperphagia-induced obesity associated with insulin resistance and dyslipidemia. Bohlooly M, et al. (medline) Diabetes. 2005 Jan;54(1):51-62. Loss of cyclin-dependent kinase inhibitors produces adipocyte hyperplasia and obesity. Naaz A, et al. (medline) FASEB J. 2004 Dec;18(15):1925-7. Epub 2004 Dec. Estrogen-related receptor alpha (ERRalpha) is a transcriptional regulator of apolipoprotein A-IV and controls lipid handling in the intestine. Carrier JC, et al. (medline) (article) J Biol Chem. 2004 Dec 10;279(50):52052-8. Epub 2004 Dec 10. The -913 G/A glutamine:fructose-6-phosphate aminotransferase gene polymorphism is associated with measures of obesity and intramyocellular lipid content in nondiabetic subjects. Weigert C, et al. (medline) J Clin Endocrinol Metab. 2004 Dec 21; [Epub ahead of print]. Direct and indirect inhibition by catecholamines of hypocretin/orexin neurons. Li Y, et al. (medline) J Neurosci. 2005 Jan 5;25(1):173-83. OTC supplements Supplement launched to moderate hunger. January 5, 2005 -- Canadian firm Vivitas this week launched a natural supplement for those who want to lose weight by simply eating less. The supplement, Satise, is designed to encourage over-eaters to consume smaller portions, by promoting a feeling of satisfaction and fullness from meals, according to the company. The company cited in a statement a study carried out in 2002 that found that portion sizes in fast food restaurants in the US are two to five times larger than they were in the 1950s. Similar research published in the Journal of the American Dietetic Association noted recently that portions of certain foods such as pasta, cereal and beverages have increased dramatically in just the last five years. Vivitas claimed that portion sizes have never been bigger and suggested that this phenomenon can encourage over-eating by as much as 56 percent. (Press release) ---- Ampalaya recognized as treatment for diabetes. January 4, 2005, Businessworld (Philippines) via NewsEdge Corporation -- The ampalaya, known in Asia for its natural ability to lower blood sugar level, is now being recognized in the international alternative medicine market as a natural treatment for type 2 diabetes. The ampalaya, through Herbcare Corp. of America, was one of the featured exhibits and among the topics of a lecture series in the 12th Annual World Congress on Anti-Aging Medicine held last month in Las Vegas, USA. Charantea ampalaya products, already a trusted brand among diabetics in Europe, was exhibited by Herbcare and Full Life Natural Options Inc., distributor of Charantea Ampalaya Dietary Supplement in the United States. (Press release) See also: Ampalaya.com. website. ---- Chemicals found in cherries may help fight diabetes. December 20, 2004 -- Perhaps George Washington wouldn't have chopped down his father's cherry tree if he knew what chemists now know. They have identified a group of naturally occurring chemicals abundant in cherries that could help lower blood sugar levels in people with diabetes. In early laboratory studies using animal pancreatic cells, the chemicals, called anthocyanins, increased insulin production by 50 percent, according to a peer-reviewed study scheduled to appear in the Jan. 5 issue of the American Chemical Society's Journal of Agricultural and Food Chemistry. ACS is the world's largest scientific society. Anthocyanins are a class of plant pigments responsible for the color of many fruits, including cherries. They also are potent antioxidants, highly active chemicals that have been increasingly associated with a variety of health benefits, including protection against heart disease and cancer. "It is possible that consumption of cherries and other fruits containing these compounds [anthocyanins] could have a significant impact on insulin levels in humans," says study leader Muralee Nair, Ph.D., a natural products chemist at Michigan State University in East Lansing. "We're excited with the laboratory results so far, but more studies are needed." Michigan is the top cherry producing state in the nation. (Press release) See also: Anthocyanins may help fight diabetes. NutraIngredients.com press release, December 21, 2004. Insulin secretion by bioactive anthocyanins and anthocyanidins present in fruits. Jayaprakasam B, et al. (medline) J Agric Food Chem. 2005 Jan 12;53(1):28-31. ---- Exercise boosts benefits of plant sterol products. December 20, 2004 -- Consuming products with plant sterols as well as exercising may offer additional benefits for those at risk of coronary heart disease, say Canadian researchers. Both consuming plant sterols and exercising have been shown to affect blood cholesterol levels on their own, they note in last month's issue of the American Journal of Clinical Nutrition. "Our research is the first to look at the complementary combined effects of these therapies," said senior author Peter Jones. The researchers from McGill University recruited 74 non-active individuals between the ages of 40 and 70 and divided them into four different groups: combination (consumed margarine containing plant sterols and exercised), exercise (consumed plant-sterol -free margarine and exercised), sterol only (consumed margarine containing plant sterols and did not exercise) and control (consumed plant-sterol free margarine and did not exercise). (Press release) Plant sterols and endurance training combine to favorably alter plasma lipid profiles in previously sedentary hypercholesterolemic adults after 8 wk. Varady KA, et al. (medline) Am J Clin Nutr. 2004 Nov;80(5):1159-66. ---- Phytopharm and Unilever enter into a licence and joint development agreement for hoodia gordonii extract. December 15, 2004 -- Phytopharm plc (LSE: PYM; NASDAQ: PHYOF) ("Phytopharm") announced today that it has granted an exclusive global licence to its Hoodia gordonii extract to Unilever plc, the global consumer products company and owner of a number of the world's leading brands. As part of the agreement, Unilever will commit to initial payments totalling approximately £6.5 million ($12.5 million) out of a potential total of £21 million ($40 million) in payments to Phytopharm. In addition Phytopharm will receive an undisclosed royalty on sales of all products containing the extract. The extract of Hoodia gordonii, a South African plant, was licensed exclusively by Phytopharm from the South African Council for Scientific and Industrial Research (CSIR) in 1997. Phytopharm has been actively developing the extract for incorporation into weight loss products. Unilever and Phytopharm will collaborate on a five stage research and development programme of safety and efficacy studies with a view to bringing new products to market. Unilever will also manage a separate agronomy programme and will support the international patent programme for the products. (Press release) See also: Unilever gains exclusive rights to Phytopharm's hoodia extract. NutraIngredients.com press release, December 15, 2004. ---- Dehydroepiandrosterone inhibits the amplification of glucocorticoid action in adipose tissue. Apostolova G, et al. (medline) Am J Physiol Endocrinol Metab. 2004 Dec 21; [Epub ahead of print]. Hepatic gene expression profiles are altered by genistein supplementation in mice with diet-induced obesity. Kim S, et al. (medline) J Nutr. 2005 Jan;135(1):33-41. Tables of contents American Journal of Clinical Nutrition. American Journal of Physiology: Endocrinology and Metabolism. Cell. Cell Metabolism. Circulation: Journal of the American Heart Association. Diabetes. Diabetes Care. Endocrinology. European Journal of Endocrinology. International Journal of Obesity. Journal of the American Dietetic Association. Journal of the American Medical Association. Journal of Clinical Endocrinology and Metabolism. Metabolism. Nature. Nature Medicine. Nature Genetics. Nutrition and Metabolism. Obesity Research. Home|Subscribe|Archives|Drug info|Contact|Media & Links|Site index|FAQs|Doctors/meetings|Admin Obesity-news is a publication of Hirsch Communications. An on-line subscription is $104.00 per year, payable in advance by check, money order, American Express, Discover, VISA or Mastercard. Subscribing is simple using our secure on-line subscription form. Obesity-news also accepts fax orders at 703/960-7462 and mail orders at PO Box 19316, Alexandria, VA 22320-0316. Copyright 1997-2008, all rights reserved. IMPORTANT: All information in this publication is believed to be accurate and true. 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