It is Saturday afternoon in Boston, it a beautiful day, the city is eagerly awaiting the second game of the Stanley Cup Championship between the Bruins and the Canucks and I am at the Boston Convention and Exhibition Center attending Endo 2011. I was very impressed after an afternoon symposium on the subject of why patients have so much trouble with avoiding weight regain.
The obesity epidemic continues unabated in the United States along with all the medical problems it engenders such as diabetes, cardiovascular disease, kidney failure and reduced longevity. In the past year, several promising drugs for obesity were turned down for approval by the FDA which continues to demand long term safety data on every anti-obesity drug it reviews. This may be a result of the Phen-Phen experience back in the mid 1990s as the the FDA’s has heightened its scrutiny of ant-obesity drugs and has made the process more difficult for a pharmaceutical company to bring a drug to market with a weight loss indication. The “toxic food environment” made famous by Kelly Brownell Phd. still is entrenched in our society with supersized caloric portions in restaurants, relentless food commercials for junk food, and fast food restaurants showing strong sales growth.
Today at Endo 2011, a symposium examined why over 70% of patients regain weight after successful weight loss efforts. The first presentation looked at the abnormal function in obese patients of the complicated communications system present in all humans which regulates the body fat store. The main players—the gut, the fat stores and the control centers in the brain—talk with each other to appropriately regulate appetite, total body energy expenditure and fat metabolism.
Ordinarily, a normal weight patient has a body weight/fat range which is kept relatively tightly controlled, particularly on the lower weight end of a “body weight zone.” So if a person weighs 150 and his weight drops to 145, the brain detects this and ramps up his appetite, reduces energy expenditure of the body and signals that energy should be stored as fat. Shortly, weight returns to 150 pounds. If the person gains an extra 5 pounds and is now 155 pounds, the opposite happens, as the command centers in the central nervous system decrease appetite, increase body energy expenditure and direct that fat be broken down and normal weight is restored back to 150 in a short time.
The problem, it seems, for patients who have become overweight or obese is that the body becomes “set” at a higher weight zone than the one achieved after dieting and losing some weight in body fat. Several physiologic adjustments by the body to weight loss have been elucidated which demonstrate the reason for the difficulty a person has to hold on to the lower weight. After weight loss, the body goes into “economy” mode by decreasing basal and total energy consumption. Muscles become more efficient in doing the same work by switching from a high energy usage muscle fiber of strength, to a special muscle fiber designed for efficiency, endurance and preservation of energy.
There is also suppression of the satiety signal sent by the stomach to the brain which fails to reduce hunger while eating and more food is consumed. All of this puts a successful weight loss effort in jeopardy as the body can do more on less energy. The body also craves more food. It is as if overnight your car went from 19 miles per gallon to 45 miles per gallon. If the person does not reduce calories and intensify energy expenditure weight regain will be inevitable. Research is implicating the hormone Leptin as playing a significant role in all of this. Leptin ordinarily is produced by the fat cells and it increases as body fat increases. Leptin tells the brain “there is too much fat” in the body. The brain responds by speeding up metabolism, burning more calories, suppressing hunger and the net effect is weight loss and avoidance of excess storage of body fat.
However, in obese subjects, Leptin signaling is disrupted and the brain does not sense the message of increased body Leptin, which results in increased body fat. There is Leptin “resistance.” So when weight loss occurs and Leptin falls, the brain really has trouble as it sees even less Leptin than is present and interprets this as a “no fat storage” condition which is an emergency. The brain slows the metabolism, increases appetite and makes muscle energy expenditure very efficient.
Intense research is under way now to understand the mechanism of Leptin résistance. Exercise is one way to overcome it. Research on the most successful weight loss patients, those in the National Weight Registry, who have lost at least 30 pounds and maintained it for over 1 year, reveals that they have discovered the necessity to become relentless exercisers in order to avoid weight regain. The American College of Sports Medicine recommends between 250-300 minutes per week of moderately intense exercise. Some combination of decreasing calories and increasing energy utilization is necessary to avoid weigh regain after a successful weight loss effort. Moreover, studies are ongoing on the mechanism of Leptin resistance and how to reverse it. One part of the solution is some critical amount of daily exercise after a weight loss effort.
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