Effects of pair-feeding and growth hormone treatment on obese transgenic rats

Abstract

BACKGROUND: It has been shown that GH-deficient subjects tend to have fat accumulation. We have produced human GH (hGH) transgenic rats that exhibit low circulating hGH levels and hyperphagia. These rats are also characterized by severe obesity, hyperinsulinemia and hyperlipidemia. OBJECTIVE: The present study was conducted in order to elucidate how excess caloric intake and impaired GH secretion account for fat accumulation and metabolic abnormalities in the transgenic rats. DESIGN AND METHODS: The transgenic rats were subjected to either pair-feeding with non-transgenic controls or hGH treatment from 4 to 12 weeks of age, and the effects on fat accumulation and some metabolic parameters were assessed. RESULTS: At the age of 12 weeks, body weight and food intake were greater in transgenic than in control rats by 10% and 27% respectively. The ratio of epididymal white adipose tissue weight to body weight (WAT/BW) was more than three times greater in transgenic than in control rats. Although pair-feeding for 8 weeks decreased body weight, it did not affect the WAT/BW ratio. Treatment with hGH affected neither body weight nor food intake, while it reduced the WAT/BW ratio by 30%. Serum concentrations of triglyceride, free fatty acid, insulin and leptin were all significantly higher in the transgenic than in the control rats. Pair-feeding decreased serum triglyceride, insulin and leptin levels, but not serum free fatty acid levels. On the other hand, hGH treatment decreased only serum leptin concentrations. CONCLUSIONS: These results suggest that severe fat accumulation in the transgenic rats mainly resulted from the decreased lipolytic action of GH, while metabolic abnormalities mainly resulted from excess caloric intake.