Central infusion of leptin into well-fed and undernourished ewe lambs: effects on feed intake and serum concentrations of growth hormone and luteinizing hormone

Leptin has been implicated in the regulation of feed intake, growth, and reproduction. The objective of this study was to determine if centrally administered leptin would affect feed intake and the secretion of growth hormone (GH) and luteinizing hormone (LH) in ewe lambs. Eighteen ewe lambs were ovariectomized and fitted with intracerebroventricular (i.c.v.) cannulae. Lambs were randomly assigned to receive either a maintenance diet (fed), or a diet that provided 38% of maintenance requirements (diet-restricted) for 14 weeks. Subsequently, recombinant ovine leptin or vehicle was continuously infused, via i.c.v. cannulae, in a linearly increasing dose for 8 days, reaching a maximum of 1.25 mug/kg per h. Feed intake was recorded on days -1 to 7. Blood was collected via jugular cannulae every 10 min for 4 h on days 0, 2, 4, 6 and 8 for the determination of serum leptin, insulin, LH and GH. Leptin suppressed feed intake in fed lambs on days 4 to 7 (P<0.001), but had no effect on feed intake in diet-restricted lambs (P>0.25). Fed lambs had greater serum concentrations of leptin than diet-restricted lambs (P=0.007). Also, although not different on day 0 (pretreatment), on day 8 serum leptin concentrations were greater in leptin-treated lambs than in saline-treated lambs (P=0.003). Insulin was lower in diet-restricted than in fed lambs (P=0.003), but was not affected by leptin treatment (P=0.82). LH pulse frequencies were lower in diet-restricted lambs than in fed lambs (P=0.038), but were not affected by leptin treatment (P=0.85). Mean serum GH was greater in diet-restricted than in fed lambs (P<0.01). In diet-restricted lambs treated with leptin or saline, mean GH did not differ on day 0, but increased in response to leptin treatment (P<0.006). Treatment of fed lambs with leptin did not affect serum GH (P>0.32). From this work, we propose that leptin represents an important functional link between adipose stores and hypothalamic function in ruminants. We demonstrate that leptin concentrations change in response to reduced nutritional status, and that leptin has the ability to regulate multiple physiological processes in lambs, including both feed intake and secretion of GH.