Increased expression of mRNA for the long form of the leptin receptor in the hypothalamus is associated with leptin hypersensitivity and fasting

被引:148
作者
Baskin, DG
Seeley, RJ
Kuijper, JL
Lok, S
Weigle, DS
Erickson, JC
Palmiter, RD
Schwartz, MW
机构
[1] Dept Vet Affairs Puget Sound Hlth Care Syst, Res Serv, Div Endocrinol & Metab, Seattle, WA 98108 USA
[2] Univ Washington, Dept Med, Seattle, WA USA
[3] Univ Washington, Dept Psychol, Seattle, WA 98195 USA
[4] Univ Washington, Dept Biol Struct, Seattle, WA 98195 USA
[5] Univ Washington, Dept Biochem, Seattle, WA 98195 USA
[6] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA
[7] Zymogenet Inc, Seattle, WA 98105 USA
关键词
D O I
10.2337/diabetes.47.4.538
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The responsiveness of the hypothalamus to the inhibitory effects of leptin on food intake and body weight is influenced by multiple factors, including deficiency of either leptin or leptin receptors (Ob-R). To investigate whether altered expression of Ob-R in the hypothalamus could potentially contribute to altered leptin sensitivity, rye performed in situ hybridization with riboprobes that detected either mRNAs encoding both the long (Ob-Rb) and short (Ob-Ra) splice variants or mRNA encoding only Ob-Rb. In the arcuate nucleus, mRNA encoding Ob-Rb, the predominant signaling form of the receptor, was 2.3 times greater in obese db/db and ob/ob mice than in lean +/ob controls (P < 0.01). In ob/ob mice, systemic administration of leptin reduced Ob-Rb mRNA content of the arcuate nucleus by 30% compared with saline-treated, pair-fed controls (P < 0.05). A 48-h fast increased Ob-Rb mRNA levels in the arcuate nucleus of normal and neuropeptide Y (NPY)-knockout mice (P < 0.01), although the effect was greater in the NPY-knockout mice (400 vs. 247%, P < 0.05). In addition, Ob-Rb mRNA hybridization was elevated by 40% in the arcuate nucleus (P < 0.05) and by 75% in the ventromedial nucleus (P < 0.05) of rats fasted 48 h. The results suggest that expression of Ob-Rb mRNA in the hypothalamus is sensitive to genetic and physiological interventions that alter circulating leptin levels, and that overexpression of Ob-Rb in the hypothalamus may contribute to increased leptin sensitivity.
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收藏
页码:538 / 543
页数:6
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