Disruption of the chemokine-like receptor-1 (CMKLR1) gene is associated with reduced adiposity and glucose intolerance.

Abstract

Adipose tissue secretes a variety of bioactive signaling molecules, termed adipokines, which regulate numerous biological functions including appetite, energy balance, glucose homeostasis, and inflammation. Chemerin is a novel adipokine that regulates adipocyte differentiation and metabolism by binding to and activating the G protein-coupled receptor, chemokine like receptor-1 (CMKLR1). In the present study, we investigated the impact of CMKLR1 deficiency on adipose development, glucose homeostasis, and inflammation in vivo. Herein we report that regardless of diet (low or high fat), CMKLR1(-/-) mice had lower food consumption, total body mass, and percent body fat compared with wild-type controls. CMKLR1(-/-) mice also exhibited decreased hepatic and white adipose tissue TNFα and IL-6 mRNA levels coincident with decreased hepatic dendritic cell infiltration, decreased adipose CD3+ T cells, and increased adipose natural killer cells. CMKLR1(-/-) mice were glucose intolerant compared with wild-type mice, and this was associated with decreased glucose stimulated insulin secretion as well as decreased skeletal muscle and white adipose tissue glucose uptake. Collectively these data provide compelling evidence that CMKLR1 influences adipose tissue development, inflammation, and glucose homeostasis and may contribute to the metabolic derangement characteristic of obesity and obesity-related diseases.

• Authors: Matthew C Ernst, Ian D Haidl, Luis A Zúñiga, Helen J Dranse, Jillian L Rourke, Brian A Zabel, Eugene C Butcher, Christopher J Sinal
• Journal: Endocrinology (Endocrinology) Vol. 153 Issue 2 Pg. 672-82 (Feb 2012) ISSN: 1945-7170 [Electronic] United States
• PMID: 22186410 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Adiponectin
• Blood Glucose
• CMKLR1 protein, mouse
• Cytokines
• Dietary Fats
• Insulin
• Leptin
• Receptors, Chemokine
• Receptors, G-Protein-Coupled
• Glucaric Acid

Topics

• Adiponectin (metabolism)
• Adipose Tissue, White (metabolism)
• Adiposity (genetics, physiology)
• Animals
• Blood Glucose
• Body Weight (genetics)
• Cytokines (genetics, metabolism)
• Dietary Fats
• Eating (genetics)
• Gene Expression Regulation (physiology)
• Glucaric Acid (metabolism)
• Glucose Intolerance (genetics, metabolism)
• Insulin (metabolism)
• Insulin Resistance
• Leptin (metabolism)
• Liver (metabolism)
• Mice
• Mice, Knockout
• Receptors, Chemokine
• Receptors, G-Protein-Coupled (genetics, metabolism)