The regulation of IGF-1 by leptin in the pig is tissue specific and independent of changes in growth hormone.
A combination of in vivo and in vitro experiments were performed to determine the extent to which exogenous leptin regulates serum growth hormone (GH) and insulin-like growth factor I (IGF-1) concentrations, and the abundance of IGF-1 mRNA in major peripheral tissues. Initially (Experiment 1), a recombinant human leptin analog was administered i.m. to young growing pigs (approximately 27 kg body weight) for 15 days at 0 (control), 0.003, 0.01 and 0.03 mg. kg(-1). day(-1). Although there was no sustained effect of leptin on serum GH, there was a reduction (P < 0.02) in serum IGF-1 at the intermediate dose that paralleled a decrease (P < 0.09) in hepatic IGF-1 expression. Leptin, at these doses, did not reduce feed intake (P > 0.57), nor was there an effect of leptin on dietary nitrogen retention (P > 0.97). In a second experiment, pigs were injected with vehicle or a higher dose of leptin (0.05 mg. kg(-1). day(-1)) for 14 days. A third treatment group was injected with vehicle and pair-fed to the intake of the group treated with leptin. In this study, exogenous leptin resulted in a sustained increase in serum leptin (P < 0.0001) and reduction in feed intake of approximately 30% (P < 0.0001). Serum IGF-1 was depressed in both the leptin-treated and pair-fed groups, relative to the group allowed ad-libitum intake (P < 0.01). Furthermore, there was no difference among treatments in the relative abundance of IGF-1 mRNA in skeletal muscle (P > 0.42) or adipose tissue (P > 0.26), and liver mRNA abundance was actually increased (P < 0.01) by leptin, despite the lower feed intake. Finally, to determine whether leptin altered the secretion of IGF-1 by isolated pig hepatocytes, primary cultures were incubated with leptin for 24 to 48 hr (Experiment 3). Leptin (100 nM) caused a sharp reduction (P < 0.0001) in dexamethasone-induced IGF-1 secretion at 24 hr (47% reduction) and at 48 hr (40% reduction). Collectively, these data indicate that leptin may regulate hepatic IGF-1 production in the pig, independent of GH, but that hepatocyte sensitivity to leptin may be depend on dose and in vitro vs. in vivo conditions.
D000273:Adipose Tissue / Q000737:chemistry; D000818:Animals; D002478:Cells, Cultured; D004435:Eating / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D013006:Growth Hormone / Q000097:blood*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis* / Q000235:genetics* / Q000378:metabolism; D020738:Leptin / Q000031:analogs & derivatives / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D013552:Swine
D020738:Leptin; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone