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| THE LATEST IN OBESITY RESEARCH AND WEIGHTLOSS DRUG DEVELOPMENT |
Volume 4, Issue 9 MERIDIA AND XENICAL: BETTER TOGETHER?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, VISA or Mastercard on our secure server. We also take credit card orders by fax at 703/960-7462. Contents
We've all heard that individuals who maintain weight loss are scarcer than hens teeth -- and this may still be the case. But among those who do maintain weight loss, it becomes easier to keep it off over the long term, according to the latest research to come out of the National Weight Control Registry. Weight maintenance percentages still low.First the bad news. The number of individuals who successfully maintain weight loss over a three year period is still dismally low, according to a population based study of 854 subjects from the Pound of Prevention Study in Minneapolis/St. Paul, Minnesota. The study investigated the effect of intervention on weight-related behaviors and mean change in body weight. Only 96 subjects (4.6 percent) lost 5 percent or more of their BMI during the first year of the study, and of those 39 (40.6 percent) successfully maintained that weight loss for another 2 years. The statistics for avoiding weight gain were more encouraging. Three hundred ninety-subjects did not gain any weight at the 1 year follow-up, and of those 209 (52.8 percent) successfully maintained their weight for another 2 years. Overall 24.5 percent of subjects in the program were successful in preventing weight gain at 3 years. Analysis of the results showed that successful weight maintenance was not associated with age, education, marital status, ethnicity, BMI at one year follow-up, percentage of fat intake, amount of TV watching, or whether subjects had intentionally tried to lose or maintain weight loss. What did work? Increased physical activity and fewer meals eaten in fast food restaurants. Health habits and weight.So what did work? It appears to be more of a mind set than a plan, according to Mary Klem of the National Weight Control Registry. Nine hundred thirty-one subjects (738 women and 173 men) from the registry who had sustained weight losses of at least 30 pounds for two years or longer said that it just got easier to maintain the weight loss over time. As the new lifestyle became second nature, they used time consuming weight control strategies like keeping records of food intake or exercise less frequently. Because the registry is comprised of those who have successfully maintained weight, it is unknown why others who lose weight gain it back. Klem hypothesized, "It is possible that, among individuals who lose weight, those who initially find maintenance to be taxing and unpleasurable may be less likely to continue to maintain their weight losses, and so may not be represented in the registry."
A new gene discovery may explain why some individuals are relatively normal weight, but pudgy -- even though they do not eat a lot. Scientists at the University of Washington have found that mice lacking the melanocortin-3 receptor (MCR-3) are normal weight but have increased fat mass, decreased lean body mass, and store food more efficiently.
A high fat diet predisposes mutant mice to obesity. In the experiments, mice maintained on a regular diet were hypophagic (ate less) although they stored food more efficiently. But when given a high fat diet, they ate more and gained more weight than wild type or MCR-3 +/- mice fed the same diet. The mechanism of the increased food efficiency is not clear, but MCR-3 knockout mice are relatively inactive, which may explain the prevalence for obesity. Mutations in both MCR-3 and MCR-4 exacerbates obesity. Mice lacking both MCR-3 and MCR-4 receptors are hyperphagic unlike MCR-3 deficient mice which eat less leading investigators to hypothesize that the excessive eating caused by the MCR-4 mutation, combined with efficient calorie storage caused by the absence of MCR-3 receptors result in fatter animals.
A "thrifty" genotype. Indications are that the MCR-3 mutation is part of a thrifty genotype, a variation that evolved to promote fat storage and increase the chances of survival in nomadic populations that were exposed to cycles of feast or famine. Unlike the leptin receptor, MCR variations do not impair fertility, thereby protecting the survival of the species. This may explain why there is a relatively high prevalence of MCR-4 mutations in obese populations (approximately 4 percent). The MCR-4 mutation is the only known form of dominantly inherited obesity in humans. Although initial research does not show a correlation between the MCR-3 mutation and obesity, further investigation is needed. Melanocortin receptors are promising candidates for anti-obesity medications. MCR-4 agonists should decrease food intake, and MCR-3 agonists feed efficiency. Together they should have a synergistic effect to suppress appetite and increase metabolic rate.
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