Hormone Wants To Keep Body At Weight Set Point

"Most studies have analyzed physical levels of ghrelin in obese or anorexic subjects," says Heather J. Leidy, who recently received her Ph.D. in physiology. "We looked at ghrelin in healthy, normal weight women. We are trying to see how the body maintains weight and maintains its energy balance."

Prior research showed that ghrelin levels rise when fasting and fall when the subject is fed. The levels rise 60 to 30 minutes before a normal meal time and 30 to 60 minutes after a meal, the level drops. According to Leidy, studies in human and rodents have found that injections of ghrelin significantly increase both hunger and food intake.

The researchers, led by Nancy I. Williams, associate professor of kinesiology, wanted to determine if ghrelin release was associated with body weight, physical exercise, reduced food intake or an overall energy deficit.

"Changes in ghrelin appear to be most sensitive to changes in body weight created by an overall energy deficit, independent of specific effects of reduced food intake or physical exercise," the researchers reported in a recent issue of the journal, Clinical Endocrinology & Metabolism.

The researchers, who also included J.K. Gardner, research associate; B.R. Frye, graduate student; and M.L. Snook, M.K. Schuchert, and E.L. Richard, undergraduate students, looked at healthy women without eating disorders, between the ages of 18 and 30, weighing between 105 and 160 pounds with 15 to 30 percent body fat. The women were non-smokers, not taking hormonal contraceptives and had no significant weight loss or gain in the past year. The study was part of a larger one designed to assess changes in reproductive function in response to controlled feeding and exercise.

Participants had to agree to eat only food provided by the Penn State General Clinical Research Center at University Park and to eat two of their three meals at the facility. In the initial study, researchers studied all participants for about a month to establish a baseline; the subjects followed the controlled diet and exercise plans for three months. Researchers randomly assigned women to four groups, a control group that did no exercise and were given enough calories to maintain their weight, a group that exercised but were given enough calories to maintain their weight, and two groups that exercised but were given fewer calories than required to maintain their weight. One energy deficit group had a moderate energy deficit and the other had a high-energy deficit.

For the ghrelin study, the four groups were compressed to three: the control group, the weight stable exerciser group and the weight loss exerciser group. Because the participants' diets were closely controlled, those that exhibited a weight loss, clearly experienced an energy deficit caused by exercise.

The researchers measured body fat, fat mass and fat-free mass before the study, at the study midpoint and after the study. They also measured resting metabolic rate and maximal aerobic capacity. Blood samples to measure ghrelin level were done on 22 subjects and midpoint measurements on 17 subjects.

"The disruption of body weight regulation seen in obesity makes one examine physiological factors in short and long term energy balance," says Leidy. "This is the first study to show that weight loss resulting from a diet and exercise intervention leads to an increase in circulating ghrelin in normal weight, healthy young women. We found that ghrelin was significantly elevated with weight loss in exercising subjects."

The researchers found that changes in ghrelin came after changes in body weight, composition and resting metabolic rate. Previous research showed that ghrelin levels are low in obese subjects and high in anorexic subjects, however, in the study's normal women, no correlation between baseline ghrelin and body weight, body mass index, percent body fat, fat mass or fat-free mass was found. The researchers state that ghrelin levels reflect energy status and body composition only in subjects who have experienced significant alterations in energy status rather than the relatively stable energy and body composition status of the study's subjects.

"The stimulatory effect on food intake attributed to ghrelin suggests a potential role for ghrelin in returning the body to a prior set-point for body weight after weight loss," the Penn State researchers report. "The absence of changes in ghrelin in our weight stable group demonstrates that exercise training itself has little impact on at least one powerful modulator of food intake."

"The increase in ghrelin in the weight loss group was in response to the overall energy deficit created by the combination of reduced food intake and exercise, and not due to the endocrine and/or metabolic effects of physical exercise itself," says Leidy.

The National Institutes of Health supported this research.