Title: Leptin antagonist reveals leptin still functions in obese rats
Abstract: Aged-obese F344xBN rats have reduced hypothalamic leptin signaling and are refractory to exogenous leptin, and hence considered leptin resistant. We hypothesized that the consequences of a leptin antagonist would be diminished or absent in rats already leptin resistant. Hypothalamic leptin signaling was assessed 1 hr after leptin (100ng), leptin (100ng) plus antagonist (5ug or 20ug), or vehicle (icv, lateral ventricle). Leptin increased phosphorylated STAT3 (P-STAT3) by 4-fold, which was fully blocked by co-administration of either dose of antagonist. Young (5m) and aged-obese (24m) were infused with antagonist (25 ug/day, lateral ventricle) or vehicle by mini pump for 7d. Cumulative food intake increased over control in both young (28.2±9.5g) and aged-obese (18.2±7.9g) as did body weight (16.4±6.4g;10.2±2.2). Adiposity was elevated, but only significant in young. These data indicate that, although diminished, the orexigenic-like effects of a leptin antagonist are qualitatively similar in lean leptin-responsive and aged-obese leptin resistant rats suggesting that leptin maintains a energy homeostatic role even in moderately obese animals. VA Medial Research and NIH, AG20985.
Publication Year: 2006
Publication Date: 2006-03-01
Language: en
Type: article
Indexed In: ['crossref']
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