GH receptor-binding protein gene disrupted mice GHR(−/−) are dwarf, obese, insulin sensitive, and long-lived whereas GH transgenic mice are giant, glucose intolerant, lean, and short lived. When challenged with a high-fat (HF) diet, all mice became hyperinsulinemic with similar percent weight gains and increases in percent body fat and size of the epididymal, retroperitoneal, and subcutaneous fat depots. For GH mice, the increase in adipose tissue was relatively small compared with WT or GHR(−/−) mice suggesting resiliency to diet-induced obesity. Together, these results support a role for GH in energy balance regulation and nutrient partitioning.
Additionally, GH has been used previously to treat individuals with type 2 diabetes with two reports showing beneficial effects on glucose metabolism. However, concerns over GHs diabetogenic action complicate its anticipated use for these patients. Thus, preclinical animal studies could help evaluate the effects of GH for treating obesity induced type 2 diabetes. In this regard, male C57BL/6J mice were placed on a HF diet to induce obesity and type 2 diabetes. Following induction and starting at 16 weeks of age, mice were treated once daily for 6 weeks with one of four GH doses. Body weight, body composition, fasting blood glucose, insulin, glucose tolerance, liver triacylglycerol, tissue weights, and blood chemistries were determined.
Body composition measurements revealed a GH dose-dependent decrease in fat and an increase in lean mass. The subcutaneous and mesenteric fat depots were most sensitive to GH treatment. In addition, GH treatment resulted in improvement in glucose metabolism, with the highest dose normalizing glucose, glucose tolerance and liver triacylglycerol. In contrast, insulin levels were not altered by GH treatment, nor did organ weights change. However, fasting plasma leptin and resistin were significantly decreased after GH treatment. Thus, GH therapy improves glucose metabolism in this mouse model of obesity and type 2 diabetes.