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

被引:72
作者
Czyzyk, Traci A. [1 ]
Nogueiras, Ruben [2 ,4 ]
Lockwood, John F.
McKinzie, Jamie H.
Coskun, Tamer
Pintar, John E. [3 ]
Hammond, Craig
Tschop, Matthias H. [2 ]
Statnick, Michael A.
机构
[1] Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA
[2] Univ Cincinnati, Dept Med, Div Endocrinol, Metab Dis Inst, Cincinnati, OH 45221 USA
[3] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, Piscataway, NJ 08854 USA
[4] Univ Santiago de Compostela, Dept Physiol, Inst Invest Sanitaria, Santiago De Compostela, Spain
基金
美国国家卫生研究院;
关键词
malonyl CoA; corticosterone; hepatocytes; energy expenditure; nonexercise activity thermogenesis; INDUCED OBESITY; MESSENGER-RNA; FOOD-INTAKE; PARAVENTRICULAR NUCLEUS; PREFRONTAL CORTEX; DEFICIENT MICE; MOUSE-BRAIN; MALONYL-COA; DYNORPHIN; RAT;
D O I
10.1096/fj.09-143610
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 kappa-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 beta-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.-Czyzyk, T. A., Nogueiras, R., Lockwood, J. F., McKinzie, J. H., Coskun, T., Pintar, J. E., Hammond, C., Tschop, M. H., Statnick, M. A. kappa-Opioid receptors control the metabolic response to a high-energy diet in mice. FASEB J. 24, 1151-1159 (2010). www.fasebj.org
引用
收藏
页码:1151 / 1159
页数:9
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