To Find the Neural Secret of Obesity

Barry E. Levin, MD, Professor and Vice Chair, New Jersey Medical School Department of Neurosciences, and Assistant Chief, Neurology Services at the VA Medical Center, began studying obesity as a medical resident at Cornell University.

At the base of the hypothalamus in the brain are neurons which are supposed to do very little else but worry about how much fat we have on our bodies. These neurons regulate energy homeostasis and take cues from the hormone leptin, which is made in fat and circulates in the blood. "Normally, leptin is an inhibitory hormone," explains Barry E. Levin, who has been studying obesity for more than 20 years. In obese individuals, the signals leptin sends are being ignored. Heart disease, diabetes, hypertension and other major obesity-linked health risks make this neural anomaly and botched brain signaling critically important. "This isn't a cosmetic problem," Levin says. Using an animal model called diet induced obesity (DIO), Levin was among the first researchers to discover that not all creatures enjoying calorically dense diets get fat. When some strains of rats are fed a fairly typical American diet with 31 percent fat, only half will become obese. The other half won't gain weight and are literally "diet-resistant" to weight fluctuations. "Something happens in the diet-resistant rats after they've been on a high-fat, high calorie regimen for three to four days," Levin explains. They start lowering their intake until they are back down to a low-calorie level. Meanwhile, the DIOs continue eating the high energy diet. At three to four weeks, they finally reduce their calorie intake to the same level as the diet-resistant rats, but obese rats continue to gain excess weight. Basically, they become more metabolically efficient and store more calories as fat. You can't get their weight back down even if you restrict them for long periods of time. Their bodies, in effect, defend that obese weight. According to Levin, the DIO rats may have the same type of "thrifty genes" once needed for survival when humans were hunter-gatherers and storing fat was a genetically good idea for a body unable to eat regularly. Unfortunately for humans, this hereditary advantage is a health hazard in our modern society with its overabundance of highly palatable foods.