EFFECTS OF 14-DAY INFUSIONS OF GROWTH-HORMONE AND OR INSULIN-LIKE GROWTH-FACTOR-I ON THE OBESITY OF GROWING ZUCKER RATS/

The response of fat tissue to GH or insulin-like growth factor I (IGF- I) differs between humans with hypopituitarism and those with exogenou s obesity; the effects of combined GH and IGF-I administration have no t been compared in these two situations. In GH-deficient dwarf rats (w ho have a primary GH deficiency), the excessive fat deposition induced by a high fat diet is completely reversed by combined infusion of GH and IGF-I. Whether the same phenomenon would be observed in geneticall y obese Zucker rats (in whom, as in obese humans, the decrease in GH s ecretion is secondary to the obese state) remained to be determined. G rowing (6-week-old) female obese Zucker rats received a continuous sc infusion of vehicle, recombinant human GH, recombinant human IGF-I, or GH plus IGF-I for 14 days (3 mg/kg day for both GH and IGF-I). Combin ed GH and IGF-I stimulated body weight gain and growth in naso-anal le ngth to the same extent as IGF-I alone, whereas GH alone was less pote nt. Because all treatments stimulated weight and linear growth proport ionately, the progression of obesity was similar in treated and contro l animals. However, GH plus IGF-I (but not either agent alone) induced a 25% decrease in the relative weight of inguinal fat. GH and IGF-I e xerted distinct effects on the relative weights of liver, kidney, and spleen and on the circulating levels of IGF-I and IGF-binding protein- 3. Circulating glucose and insulin levels did not change in any group. In summary, GH plus IGF-I infusions decrease the relative weight of i nguinal fat in Zucker rats as in obese GH-deficient dwarf rats; howeve r, this effect is of more modest magnitude despite the use of a 2- to 3-fold higher dose and is limited to the inguinal site. Thus, GH plus IGF-I infusions did not influence the obesity index in Zucker rats. In asmuch as Zucker rats are a better model of childhood-onset obesity th an dwarf rats fed a high fat diet, the present results do not appear p romising for extrapolation to clinical studies in children. The mechan isms by which the primary vs. secondary nature of the decreased GH sec retion influences the effect of GH plus IGF-I on obesity remain to be determined.