κ-Opioid receptors control the metabolic response to a high-energy diet in mice

Traci A. Czyzyk, Ruben Nogueiras, John F. Lockwood, Jamie H. McKinzie, Tamer Coskun, John E. Pintar, Craig Hammond, Matthias H. Tschöp, Michael A. Statnick

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

General opioid receptor antagonists reduce food intake and body weight in rodents, but the contributions of specific receptor subtypes are unknown. We examined whether genetic deletion of the κ-opioid receptor (KOR) in mice alters metabolic physiology. KOR-knockout (KO) and wild-type (WT) mice were fed a high-energy diet (HED) for 16 wk. KO mice had 28% lower body weight and 45% lower fat mass when compared to WT mice fed an HED. No differences in caloric intake were found. An HED reduced energy expenditure in WT mice, but not in KO mice. KOR deficiency led to an attenuation of triglyceride synthesis in the liver. Malonyl CoA levels were also reduced in response to an HED, thereby promoting hepatic β-oxidation. Glycemic control was also found to be improved in KO mice. These data suggest a key role for KORs in the central nervous system regulation of the metabolic adaptation to an HED, as we were unable to detect expression of KOR in liver, white adipose tissue, or skeletal muscle in WT mice. This study provides the first evidence that KORs play an essential physiological role in the control of hepatic lipid metabolism, and KOR activation is a permissive signal toward fat storage.

Original languageEnglish (US)
Pages (from-to)1151-1159
Number of pages9
JournalFASEB Journal
Volume24
Issue number4
DOIs
StatePublished - Apr 2010

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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