Characterization of metabolic phenotypes of mice lacking GPR61, an orphan G-protein coupled receptor.

Abstract

AIMS:

GPR61 is an orphan G protein-coupled receptor whose function remains unknown. The purpose of the present study is to elucidate the importance of GPR61 in metabolism by characterization of GPR61-deficient mice.

MAIN METHODS:

Male GPR61-deficient mice were characterized regarding various metabolic parameters, including food intake, body weight, oxygen consumption, body temperature, locomotor activity, and in a pair feeding study. Hypothalamic gene expression was analyzed using real-time quantitative RT-PCR.

KEY FINDINGS:

GPR61-deficient mice exhibited marked hyperphagia and heavier body weight than wild-type mice. Hyperphagia of GPR61-deficient mice was observed before the differences in body weight became apparent between the genotypes. When body weight difference did become apparent between genotypes, increases in visceral fat pad weight, liver weight, liver triglyceride (TG) content, plasma leptin, and plasma insulin were observed in GPR61-deficient mice, suggesting that GPR61 deficiency caused obesity associated with hyperphagia. Oxygen consumption, body temperature, and locomotor activity were not significantly different between GPR61-deficient and wild-type mice. Pair-fed GPR61-deficient mice had a greater fat mass than wild-type mice despite comparable body weight in both genotypes. The mRNA levels of proopiomelanocortin (POMC) and brain-derived neurotropic factor (BDNF) in the hypothalamus of GPR61-deficient mice were significantly lower than those of wild-type mice.

SIGNIFICANCE:

GPR61-deficient mice exhibited obesity associated with hyperphagia. These findings suggest that GPR61 is involved in the regulation of food intake and body weight, and may be of importance when considering GPR61 as a therapeutic target for obesity or eating disorders.

• Authors: Hirohide Nambu, Miyuki Fukushima, Hirohiko Hikichi, Takao Inoue, Norihiro Nagano, Yoshio Tahara, Tadahiro Nambu, Junko Ito, Yoshihiro Ogawa, Satoshi Ozaki, Hisashi Ohta
• Journal: Life sciences (Life Sci) Vol. 89 Issue 21-22 Pg. 765-72 (Nov 21 2011) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 21971119 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• GPR61 protein, mouse
• Galactosides
• Indoles
• RNA, Messenger
• Receptors, G-Protein-Coupled
• Triglycerides
• 5-bromo-4-chloro-3-indolyl beta-galactoside

Topics

• Animals
• Body Composition (genetics)
• Body Temperature (genetics)
• Body Weight (genetics)
• Calorimetry, Indirect
• Diet
• Eating (genetics)
• Galactosides
• Immunohistochemistry
• Indoles
• Lac Operon
• Liver (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Motor Activity (physiology)
• Organ Size (genetics)
• Oxygen Consumption (drug effects)
• Phenotype
• RNA, Messenger (biosynthesis, genetics)
• Real-Time Polymerase Chain Reaction
• Receptors, G-Protein-Coupled (genetics, metabolism)
• Triglycerides (metabolism)