Metabolic and Endocrine Responses to Overeating.

Abstract

Although metabolic abnormalities common in obesity are well-defined, the metabolic and endocrine responses that occur in the early stages of weight gain are not. The overall objective of my dissertation was to characterize the metabolic and endocrine responses during 2 weeks of overeating. We conducted a battery of metabolic tests in a total of 23 healthy non-obese volunteers before, during, and after a 2-week overeating intervention. Subjects remained in the hospital for the entire 2-week overeating period to ensure strict control over their diet (i.e., they consumed 70kcals/kg FFM/day [~4000kcals/day]) and their physical activity (i.e., they were limited to 1500 steps per day). STUDY 1 of my dissertation examined some important metabolic adaptations to overeating, and we found that 2-weeks of overeating increased whole-body insulin resistance. However, the impaired systemic insulin sensitivity was not accompanied by changes in markers of impaired insulin action within skeletal muscle. Interestingly, muscle lipid accumulation did not increase despite consuming about twice the normal amount of dietary fat (~150 grams/day). STUDY 2 of my dissertation focused on the endocrine responses to overeating, and as anticipated we found that the large and frequent meals provided during the overeating period resulted in a chronic elevation in plasma insulin concentration (p<0.05). In STUDY 2 we report was a nearly 80% suppression in 24h growth hormone (GH) concentration. This reduction in GH was a likely a consequence of the inhibitory effects of the chronic hyperinsulinemia during overeating. In STUDY 3 we examined the metabolic consequences of this marked suppression of GH concentration. In a separate group of subjects, we provided multiple daily injections of exogenous GH during the same 2-week overeating intervention. Preventing the fall in plasma GH concentration exacerbated systemic insulin resistance and fasting lipemia was significantly increased. Therefore, the normal fall in plasma GH with overeating may actually help mitigate the rise of cardiovascular and metabolic risk factors. Overall, the findings from the three studies of my dissertation help expand our understanding about the metabolic and endocrine responses that occur in the early stages of weight gain, which may shed important light on the development obesity-related diseases.