Consumption of a high-fat diet induces central insulin resistance independent of adiposity

PHYSIOLOGY & BEHAVIOR

卷:103

Article

Clegg, Deborah J.¹  Gotoh, Koro²  Kemp, Christopher²  Wortman, Matthew D.²  Benoit, Stephen C.²  Brown, Lynda M.³  D'Alessio, David⁴  Tso, Patrick⁵  Seeley, Randy J.⁴  Woods, Stephen C.² 

[1] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Touchstone Diabet Ctr, Dallas, TX 75390 USA

[2] Univ Cincinnati, Dept Psychiat, Cincinnati, OH 45221 USA

[3] Univ N Carolina, Dept Nutr, Greensboro, NC 27412 USA

[4] Univ Cincinnati, Dept Med, Cincinnati, OH 45221 USA

[5] Univ Cincinnati, Dept Pathol, Cincinnati, OH 45221 USA

关键词: Obesity;    Insulin;    Insulin receptor;    Food intake;    Hypothalamus;   

DOI  :  10.1016/j.physbeh.2011.01.010

来源: Elsevier

【 摘 要 】

Plasma insulin enters the CNS where it interacts with insulin receptors in areas that are related to energy homeostasis and elicits a decrease of food intake and body weight. Here, we demonstrate that consumption of a high-fat (HF) diet impairs the central actions of insulin. Male Long-Evans rats were given chronic (70-day) or acute (3-day) ad libitum access to HE low-fat (LF), or chow diets. Insulin administered into the 3rd-cerebral ventricle (i3vt) decreased food intake and body weight of LF and chow rats but had no effect on HF rats in either the chronic or the acute experiment. Rats chronically pair-fed the HF diet to match the caloric intake of LF rats, and with body weights and adiposity levels comparable to those of LF rats, were also unresponsive to i3vt insulin when returned to ad libitum food whereas rats pair-fed the LF diet had reduced food intake and body weight when administered i3vt insulin. Insulin's inability to reduce food intake in the presence of the high-fat diet was associated with a reduced ability of insulin to activate its signaling cascade, as measured by pAKT. Finally, i3vt administration of insulin increased hypothalamic expression of POMC mRNA in the LF- but not the HF-fed rats. We conclude that consumption of a HF diet leads to central insulin resistance following short exposure to the diet, and as demonstrated by reductions in insulin signaling and insulin-induced hypothalamic expression of POMC mRNA. (C) 2011 Elsevier Inc. All rights reserved.

【 授权许可】

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