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 the model. Female GH-deficient dwarf rats fed a high-fat diet became obese and insulin-resistant compared with chow-fed controls. They were treated with recombinant human GH (rhGH 100-500 micrograms/day, s.c. for 14 days) by daily injection or minipump infusion with or without rhIGF-I (200 micrograms/day, sc infusion). Injections of rhGH increased body weight; infusions of rhGH caused weight loss. RhIGF-I by itself, or rhIGF-I plus GH injections had little effect, whereas rhGH infusions plus rhIGF-I caused a weight loss equivalent to the weight gained during the high-fat feeding and a decrease in fat pad weight. For some responses (serum IGF-1 and GHBP), the obese rats were GH resistant. Fat was lost from the internal fat pads when obese rats were returned to a chow diet, and injections of rhGH surprisingly attenuated this 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 GH it has antiinsulin actions causing a powerful net lipolysis. If GH plus IGF-I have similar effects in humans they may be useful for reducing body fat.
Clark
R G
RG
Genentech, Inc., South San Francisco, California 94080, USA.
Mortensen
D L
DL
Carlsson
L M
LM
Carlsson
B
B
Carmignac
D
D
Robinson
I C
IC
D000273:Adipose Tissue / Q000473:pathology*; D000818:Animals; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage; D004347:Drug Interactions; D004435:Eating / Q000187:drug effects; D005260:Female; D013006:Growth Hormone / Q000008:administration & dosage* / Q000172:deficiency* / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000494:pharmacology; D007700:Kinetics; D008066:Lipolysis / Q000187:drug effects; D009765:Obesity / Q000209:etiology / Q000473:pathology*; D051381:Rats; D011922:Rats, Mutant Strains; D011994:Recombinant Proteins / Q000008:administration & dosage; D015430:Weight Gain
D004041:Dietary Fats; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone