The regulation of energy storage by growth hormone and insulin-like growth factor-I

Energy storage in body compartments, i.e. water, protein, fat, and mineral, is affected by dietary macronutrients and by endogenous hormones. Of the macronutrients, the proportion of total calories consumed as dietary fat is most important in determining the proportion of adipose tissue to lean body mass. Of the anabolic hormones, growth hormone (GH), insulin-like growth factor-I (IGF-I), and testosterone are major regulators of growth and of distribution of energy storage among body compartments.

I used a genetic model of GH deficiency, the 'little' mouse (gene symbol lit), to study the interaction between dietary fat and these anabolic hormones to regulate energy storage in body compartments. Manipulation of the ratio of dietary fat to carbohydrate was accomplished using two isocaloric, constant protein diets, with either four or twelve percent fat. Hormones were administered by subcutaneous injections, mini-osmotic pumps, or pellets at a dose level and for a time course determined by preliminary dose-response studies to optimize the hormonal effect.

Comparison of GH-deficient lit/lit with normal $lit/+$ mice showed that the $lit/lit$ mice were characterized by abnormally large adipose tissue stores and reduced body water, protein and mineral from 2 weeks of age onward. These changes occurred despite normal energy intake, indicating that hyperphagia was not characteristic of this GH-induced obesity.

Dietary and hormonal treatment results suggested that in immature $lit/lit$ mice dietary macronutrient composition affected all four body compartments, while short term GH treatment manipulated only the body water compartment. In adult $lit/lit$ mice, dietary treatment of males affected body water and fat, but only affected carcass weight in females. GH treatment of adults induced changes in carcass weight and in all body compartments. IGF-I and testosterone treatment of adult females showed that IGF-I regulated both water and protein metabolism in an organ specific manner, whereas the effect of testosterone in specific organs was limited to protein metabolism. These studies suggest that dietary treatment of GH deficient children and adult males would complement GH therapy, but that dietary treatment of adult females may not improve GH-induced changes in body compartments.