Obesity-news.com THE LATEST IN OBESITY RESEARCH AND WEIGHTLOSS DRUG DEVELOPMENT     Join our list More information      Volume 4, Issue 3 February/March 2000 NEWS ONLY SECTION Access to full-text is available with a subscription to Obesity-news. To subscribe please fill out our subscription information form. Subscribing is easy using your American Express, Discover, VISA or Mastercard on our secure server. We also take credit card orders by fax at 703/960-7462. To order by mail, send your subscription information form to PO Box 19316, Alexandria, VA 22320-0316 with your check, money order, or credit card information. Contents In the news Gender differences in weight maintenance. Cholesterol lowering therapy and weight gain. Sibutramine: Its impact on long term metabolic rate. Obesity gene discoveries ACRP30: Its contribution to obesity and diabetes. Protein controlling fat cell development discovered. Drugs in development Amylin and weight loss. Melatonin and body weight. Green tea and weight loss. Tea for two: Obesity and PCOS. RXR:PPARs: Insulin sensitizing drugs that promote weight loss. B-3AR compound for obesity and diabetes. Leptin studies Leptin production in women with upper body obesity. Nutrition High-carb diets and triglycerides. More on diet and weight gain. Subcription Information A one year on-line subscription to Obesity-news is $104.00. Send check or money order, in US currency to: Obesity-news, PO Box 19316, Alexandria, VA 22320-0316. Or subscribe or renew on-line using American Express, Discover, VISA or Mastercard through our secure server. In the news Gender differences in weight maintenance. Because long-term prognosis of weight loss maintenance is poor, researchers have taken great interest in individuals who have succeeded. Studies, like the National Weight Control Registry, track the rare individuals who have been successful at losing excess weight and keeping it off. But these types of studies suffer from selection bias, and the number of subjects in such investigations is small. In a recent study, investigators from the Obesity Research Group at the University of Helsinki and the Department of Mental Health and Alcohol Research at the National Public Health Institute in Helsinki looked at the behaviors associated with long-term weight maintenance in subjects selected from the Finnish Twin Cohort Study, and found that the issues surrounding successful weight maintenance were gender specific. In men, medical problems were the major impetus for losing weight, and in women, social issues were more important. The results were published in the February issue of the International Journal of Obesity. subjects. Individuals from the Finnish Twin Cohort Study who were overweight (BMI >27) at baseline in 1975. Subjects were excluded for pregnancy, cancer and disability. After exclusions, the final sample consisted of 332 women and 579 men. Subjects were classified as weight loss maintainers if they had lost at least 5 percent of their body weight between 1975 and 1981 and were still at least 5 percent below their original weight in 1990. Methods. Subjects reported weight and height, and were asked to recall their weight 1 and 5 years previously, their lifetime maximum (non-pregnant) weight, weight at the ages of 20 and 30, and BMI. At baseline, subjects were asked if they were currently trying to lose weight, and in 1990 subjects were asked if they had ever dieted or tried to lose weight. Those who admitted dieting were classified as having made intentional weight loss attempts. In addition, subjects' education, employment, marital and health status, and health related behaviors were obtained via questionnaire. Indicators of well-being, such as life satisfaction, stress, sleep quality, happiness, loneliness, and other factors were also assessed. Results. Only 5.1 percent of all initially overweight women and 6.6 percent of men maintained a weight loss of at least 5 percent. The "trigger" event for losing weight, health habits and life satisfaction, differed by gender as follows: Weight loss success in men. Weight loss was associated with health related issues like diabetes, hypertension or heart disease. Weight maintaining men generally exhibited healthier life style choices than those who regained weight. They drank and smoked less, ate more vegetables, less sugar and exercised more, even before the weight loss. They also expressed more satisfaction with life, and felt less stress than men who lost and regained weight. Chronic disease explained the healthy behaviors among some maintainers. There was an increased incidence of diabetes, and higher medication use among weight maintainers. It is possible that getting diabetes or other chronic health problems initially triggered weight loss attempts or motivated maintainers to keep weight level down. Weight loss success in women. Women who maintained weight loss were less happy at baseline, and the weight loss was triggered by loneliness, and less satisfaction with life. More of the weight maintainers were living without a partner before losing weight. On the other hand, women who regained weight were married, had higher self-esteem, and were happier. The weight maintenance group had slightly more medical problems, exercised less, smoked more, and had trouble sleeping before they lost weight. Weight loss was accompanied by positive behavioral changes, resulting in improved life satisfaction, less loneliness and better physical condition. But weight maintainers continued to have problems with sleep, and used more sleeping pills, pain killers and alcohol after weight loss. It is possible that overweight women without serious health related-problems may be less motivated to maintain weight loss. Conclusion. Researchers speculate that women with excess weight are more likely to be stigmatized and disadvantaged by society than men, triggering the weight loss. It is also possible that low subjective well-being acts as a trigger. But what men and women have in common, is that there must be "rewards" of long term weight loss, be they physical or psychological. And those rewards, be they better health or better lifestyle, appear to be absent in those patients who regain weight. A descriptive study of weight loss maintenance: 6 and 15 year follow-up of initially overweight adults. Sarlio-Lahteenkorva S, et al. (medline) Int J Obes Relat Metab Disord. 2000 Jan;24(1):116-125. Obesity gene discoveries Melatonin and body weight. An age related decline in melatonin alters metabolism and spontaneous physical activity, resulting in increased body weight, visceral adiposity, and associated metabolic conditions such as glucose intolerance, insulin resistance, diabetes, lipid disorders and hypertension. However, the mechanism by which this occurs is unknown. Melatonin, a hormone produced by the pineal gland, mediates circadian rhythms and other physiological functions. But melatonin synthesis and secretion decrease significantly by middle age and decline even further through old age. In addition to its effect on biological rhythms, the decline in melatonin is associated with the increases in visceral adiposity that occur with aging, especially in men. Previous rodent studies have shown that daily administration of melatonin reduces intraabdominal fat, plasma leptin, and plasma insulin to youthful levels. In a study on Sprague Dawley rats, researchers at the University of Washington and Loma Linda University investigated the how melatonin affects food intake and suggested several mechanisms by which this may occur. The results were published in the February issue of the journal Endocrinology. Experiments. In the primary experiment, 37 middle-aged male Sprague Dawley rats were divided into two groups. One group received 0.4 µg/ml melatonin and the other placebo in their daily drinking water for 12 weeks. An additional group of 18 young rats were given placebo, and housed with the middle-aged rats. At week 12, 3 rats from each group were sacrificed. The remaining middle-aged rats were then crossed over into the alternative treatment group for an additional 12 weeks, and the remaining young rats were removed from the study. Body weight, food consumption, spontaneous activity, body temperature and body composition were measured, and blood samples of plasma melatonin levels were taken. Results. Twelve weeks of melatonin treatment in middle-aged rats decreased body weight, visceral fat, plasma leptin and plasma insulin while increasing spontaneous activity, body temperature and plasma corticosterone concentrations, without any change in food consumption. In the cross over experiment, control rats given melatonin lost weight and melatonin treated rats given placebo gained weight without any change in food intake in either group. Melatonin decreased body weight over a 2 week period, after which time weight stabilized at the lower level. In a previous study, the response of middle-aged rats to melatonin was sustained into old age. But a more recent experiment shows that young rats do not have the same response to melatonin, suggesting that the response to exogenous melatonin is dependent on the age-associated decrease in melatonin secretion. Several mechanisms by which melatonin may alter the aging process are suggested by this study: Altering hypothalamo-pituitary-adrenal regulation. Melatonin treatment restored morning plasma corticosterone levels to those of young animals, without affecting adrenal and thymus weights, indicators of chronic stress or glucocorticoid excess. This shows that melatonin may have altered some aspects of hypothalamo-pituitary-adrenal regulation in a manner not associated with a chronic stress response. Changing the body weight set-point. In both the original and cross over studies, animals given melatonin lost weight and those given placebo gained weight without a change in food intake. These results suggest that melatonin treatments influenced the animals to defend different body weight set points. Increasing metabolic rate. Feed efficiency, a measure of metabolic function, was negative in the melatonin-treated animals and positive in the controls. This finding is consistent with the observation that melatonin injections increase norepinephrine-stimulated metabolic rate in mice. Increasing spontaneous activity. Although a specific mechanism for this effect is not clear, in this and other studies, melatonin increases physical activity. The small increases in physical activity of melatonin-treated rats in this study may have contributed to their decreased body weight. Increasing body temperature. Studies on melatonin and body temperature have been inconsistent, but in these experiments melatonin treatment in middle-aged rats raised daytime body core temperature to a similar level found in young animals. Researchers postulate two theories as to how this may occur. First, that visceral adipose tissue is increased when body core temperatures are low, due to increased activity of lipoprotein lipase, an enzyme involved in fat storage. Alternatively, the increase in physical activity and body temperature may reflect increased autonomic activity, which directly regulates metabolism, especially thermogenesis in brown fat. Increasing insulin and leptin sensitivity. Although leptin and insulin sensitivity were not measured, it is reasonable to assume that the tissue responsiveness increased, consistent with decreases in circulating levels of these hormones. The results on rats may not apply to other species, and the effects of daily melatonin administration on energy balance in humans have not been determined. The mechanisms by which melatonin administration may reverse or prevent age related metabolic changes are being further investigated. Daily melatonin administration to middle-aged male rats suppresses body weight, intraabdominal adiposity, and plasma leptin and insulin independent of food intake and total body fat. Wolden-Hanson T, et al. (medline) Endocrinology 2000 Feb;141(2):487-97. See also: Daily melatonin administration at middle age suppresses male rat visceral fat, plasma leptin, and plasma insulin to youthful levels. Rasmussen DD, et al. (medline) Endocrinology 1999 Feb;140(2):1009-12. Nutrition More on diet and weight gain. Why can some people eat a tray of McDonald's burgers and not gain an ounce, while others gain weight eating a salad? This has been a question that has challenged scientists, and while some answers have been found, most of the reasons remain largely unknown. The animal model that most closely resembles human obesity is the DIO rat. Like humans, rats with diet induced obesity (DIO) are predisposed to become obese when they eat a highly-palatable high-fat diet. They also develop insulin resistance, have lower growth hormone levels, and a propensity to metabolize carbohydrate preferentially over fat. Unlike the mahogany mouse, pictured below, diet induced obesity is inherited through a variety of unknown "susceptibility genes". About half of Sprague-Daley rats fed a high energy diet develop DIO, whereas the others gain no more weight than rats eating a normal diet. When DIO rats are calorie restricted they reduce their metabolic rate, and return to their previously high body weight after the restriction is discontinued. Diet resistant animals, like the mahogany mouse, do not gain weight even when they overeat. In an effort to find out how DIO rats differ from their diet resistant cousins, Barry E. Levin and colleagues at New Jersey Medical School in Newark, New Jersey conducted a set of experiments on chronic caloric restriction and refeeding. The results published in the January issue of the American Journal of Physiology: Regulatory, Integrative and Comparitive Physiology. Experiments. 60 male Sprague-Dawley rats were fed a high-energy diet for 2 weeks. The 24 rats with the highest body weight gain were designated as DIO, the 24 with the lowest weight gain were designated as diet resistant (DR), and the remaining 12 intermediate weight gainers were switched back to chow and used as controls. The DIO and DR rats were then maintained on the high-energy diet for another 8 weeks. In the caloric restriction phase, 12 of the DIO and 12 of the DR rats were restricted to 50 percent of the control diet for 5 weeks. Half of the DIO and DR rats were sacrificed after calorie restriction to measure fat pads, and the other half were given ad libitum access to chow for another ten weeks. Results and discussion By week 3 on the high-energy diet, DIO rats had significantly higher body weight, plasma leptin, insulin and fat pad weights than DR rats, and these levels remained higher for the rest of the study. DR rats weighed significantly less than the control rats throughout the weight gain period. Although they were 20 percent heavier, energy intake in the DIO rats at the end of the high-energy diet phase was not significantly different from the DR rats. During the diet restriction phase, both DIO and DR rats rapidly dropped body weight. DIO rats reduced fat depots, plasma leptin and insulin levels by 35 percent during diet restriction, whereas these levels remained the same in DR rats. When fed ad libitum at the end of the study, both sets of rats regained their body weight within 2 weeks. But this was associated with increased fat mass, leptin and insulin levels only in the DIO rats. The results of this study show that rats with diet induced obesity lose primarily fat mass under dietary restriction, whereas DR rats lose primarily lean body mass. DIO rats increase their metabolic efficiency fairly soon after exposure to a high energy diet. On the other hand, DR rats have low metabolic efficiency. Consistent with data from other studies, DIO rats have elevated sympathetic activity both before and after they become obese, and sympathetic activity falls greatly while under dietary restriction. On the other hand, the sympathetic activity of DR rats only varies slightly during weight gain and weight loss. These observations suggest that the greater the loss of body fat during a diet, the greater the degree of conservation of energy in the form of increased metabolic efficiency. Defense of body weight against chronic caloric restriction in obesity-prone and -resistant rats. Levin BE, et al. (medline) Am J Physiol Regul Integr Comp Physiol. 2000 Jan;278(1):R231-R237. 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. 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