New Hormone Provides Clues About Weight Loss

The recently identified hormone ghrelin increases hunger and food intake in almost everyone—except people who have undergone gastric bypass surgery for obesity. Researchers believe that reduced levels of ghrelin may be one means by which bypass patients lose substantial amounts of weight; the surgery also restricts the amount of food a person can eat and bypasses sections of the stomach and small intestine so fewer nutrients are absorbed.

Ghrelin, produced primarily by the stomach and duodenum (the first part of the small intestine), increases food intake by contributing to mealtime hunger. Levels of the hormone in the blood rise shortly before and fall shortly after every meal. Researchers at the University of Washington in Seattle hypothesized that ghrelin levels would go up as a result of diet-induced weight loss, leading to increased appetite and weight regain as part of the body’s attempt to compensate for the energy deficit. They further speculated that the opposite would be true for people who lost weight through gastric bypass surgery—ghrelin levels would drop because ghrelin-producing cells in the stomach have limited contact with ingested nutrients, which normally regulate levels of the hormone.

The researchers concluded that gastric restriction is not the only means by which bypass surgery patients lose weight.

To test their hypotheses, the researchers looked at ghrelin levels in three groups: obese patients who had undergone gastric bypass surgery and lost an average of 36 percent of their body weight; a control group of obese patients who had lost an average of 17 percent of body weight through dieting; and a control group of normal-weight subjects. Among those who lost weight by dieting, ghrelin levels throughout the course of the day were 24 percent higher than pre-weight-loss levels. Nevertheless, these patients maintained the same pattern of daily fluctuation as the control group, with levels rising before and falling after each meal.

Ghrelin levels in the gastric bypass surgery patients, on the other hand, dropped to 72 percent below levels among the obese controls and 77 percent below levels among the normal-weight controls. In addition, bypass patients did not show meal-related fluctuations in ghrelin levels as did the other two groups.

The researchers concluded that gastric restriction is not the only means by which bypass surgery patients lose weight. If this were the case, patients would be expected to eat frequent small meals made up of calorie-dense foods to compensate for energy deficits. Instead, research has shown that bypass patients feel hungry less often after the operation, eat fewer meals and snacks, and voluntarily reduce their intake of calorie-dense foods. In addition, gastric bypass—the only weight-loss surgery that isolates ghrelin cells from contact with nutrients—is more effective than operations that simply reduce the size of the stomach.

Since ghrelin appears to play a part in the body’s adaptive response limiting the amount of weight people can lose through dieting, researchers may one day develop an obesity treatment that blocks ghrelin’s action.

This study, funded in part by the National Institutes of Health, appears in the May 23, 2002 issue of The New England Journal of Medicine. s