THE OBESE GROWTH-HORMONE (GH)-DEFICIENT DWARF RAT - BODY-FAT RESPONSES TO PATTERNED DELIVERY OF GH AND INSULIN-LIKE GROWTH-FACTOR-I

We describe a new animal model of obesity and GH deficiency and report the effects on body fat of administering (GH) and insulin-like growth factor (IGF-I) in this model. Female GH-deficient dwarf rats fed a hi gh-fat diet became obese and insulin-resistant compared with chow-fed controls. They were treated with recombinant human GH (rhGH 100-500 mu g/day, sc for 14 days) by daily injection or minipump infusion with o r without rhTGF-I (200 mu g/day, sc infusion). Injections of rhGH incr eased body weight; infusions of rhGH caused weight loss. RhIGF-I by it self, or rhIGF-I plus GH injections had Little effect, whereas rhGH in fusions plus rhIGF-I caused a weight loss equivalent to the weight gai ned during the high-fat feeding and a de crease in fat pad weight. For some responses (serum IGF-1 and GHBP), the obese rats were GH resista nt. Fat was lost from the internal fat pads when obese rats were retur ned to a chow diet, and injections of rhGH surprisingly attenuated thi s loss of fat. In obese dwarf rats, the lipolytic effects of rhGH are dose-regime dependent. By itself IGF-I is not insulin-like, but in the presence of GPI it has antiinsulin actions causing a powerful net lip olysis. If GH plus IGF-I have similar effects in humans they may be us eful for reducing body fat.