Signals from intra-abdominal fat modulate insulin and leptin sensitivity through different mechanisms: Neuronal involvement in food-intake regulation

Tetsuya Yamada, Hideki Katagiri, Yasushi Ishigaki, Takehide Ogihara, Junta Imai, Kenji Uno, Yutaka Hasegawa, Junhong Gao, Hisamitsu Ishihara, Akira Niijima, Hiroyuki Mano, Hiroyuki Aburatani, Tomoichiro Asano, Yoshitomo Oka

Research output: Contribution to journalArticlepeer-review

99 Citations (Scopus)

Abstract

Intra-abdominal fat accumulation is involved in development of the metabolic syndrome, which is associated with insulin and leptin resistance. We show here that ectopic expression of very low levels of uncoupling protein 1 (UCP1) in epididymal fat (Epi) reverses both insulin and leptin resistance. UCP1 expression in Epi improved glucose tolerance and decreased food intake in both diet-induced and genetically obese mouse models. In contrast, UCP1 expression in Epi of leptin-receptor mutant mice did not alter food intake, though it significantly decreased blood glucose and insulin levels. Thus, hypophagia induction requires a leptin signal, while the improved insulin sensitivity appears to be leptin independent. In wild-type mice, local-nerve dissection in the epididymis or pharmacological afferent blockade blunted the decrease in food intake, suggesting that afferent-nerve signals from intra-abdominal fat tissue regulate food intake by modulating hypothalamic leptin sensitivity. These novel signals are potential therapeutic targets for the metabolic syndrome.

Original languageEnglish
Pages (from-to)223-229
Number of pages7
JournalCell Metabolism
Volume3
Issue number3
DOIs
Publication statusPublished - 2006 Mar

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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