kappa-Opioid receptors control the metabolic response to a high-energy diet in mice.
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., Tschöp, M. H., Statnick, M. A. kappa-Opioid receptors control the metabolic response to a high-energy diet in mice.
Czyzyk
Traci A
TA
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, DC 0403, 355 E. Merrill St., Indianapolis, IN 46285, USA. czyzyk-morgantr@lilly.com
Nogueiras
Ruben
R
Lockwood
John F
JF
McKinzie
Jamie H
JH
Coskun
Tamer
T
Pintar
John E
JE
Hammond
Craig
C
Tschöp
Matthias H
MH
Statnick
Michael A
MA
D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000235:genetics; D002149:Energy Intake; D005786:Gene Expression Regulation / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics; D010084:Oxidation-Reduction; D017473:Receptors, Opioid, kappa / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000096:biosynthesis*
D017473:Receptors, Opioid, kappa; D014280:Triglycerides