Impaired CNS leptin action is implicated in depression associated with obesity

Nobuko Yamada, Goro Katsuura, Yukari Ochi, Ken Ebihara, Toru Kusakabe, Kiminori Hosoda, Kazuwa Nakao

研究成果: Article査読

187 被引用数 (Scopus)

抄録

Recent epidemiological studies indicate that obesity increases the incidence of depression. We examined the implication of leptin for obesity-associated depression. Leptin induced antidepressive behavior in normal mice in a forced swimming test (FST), and leptin-overexpressing transgenic mice with hyperleptinemia exhibited more antidepressive behavior in the FST than nontransgenic mice. In contrast, leptin-deficient ob/obmice showed more severe depressive behavior in the FST than normal mice, andleptin administration substantially ameliorated this depressive behavior. Diet-induced obese (DIO) mice fed a high-fat diet showed more depressive behavior in the FST and in a sucrose preference test compared with mice fed a control diet (CD). In DIO mice, leptin induced neither antidepressive action nor increment of the number of c-Fos immunoreactive cells in the hippocampus. Diet substitution from high-fat diet to CD in DIO mice ameliorated the depressive behavior and restored leptin-induced antidepressive action. Brain-derived neurotrophic factor concentrations in the hippocampus were significantly lower in DIO mice than in CD mice. Leptin administration significantly increased hippocampal brain-derived neurotrophic factor concentrations in CD mice but not in DIO mice. The antidepressant activity of leptin in CD mice was significantly attenuated by treatment with K252a. These findings demonstrated that leptin induces an antidepressive state, and DIO mice, which exhibit severe depressive behavior, did not respond to leptin in both the FST and the biochemical changes in the hippocampus. Thus, depression associated with obesity isdue, at least in part, to impaired leptin activity in the hippocampus.

本文言語English
ページ(範囲)2634-2643
ページ数10
ジャーナルEndocrinology
152
7
DOI
出版ステータスPublished - 2011 7月

ASJC Scopus subject areas

  • 内分泌学

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