Disruption of the Chemokine-Like Receptor-1 (CMKLR1) Gene Is Associated with Reduced Adiposity and Glucose Intolerance

• Published in: Endocrinology (Philadelphia) 2012-02, Vol.153 (2), p.672-682
• Main Authors: Ernst, Matthew C, Haidl, Ian D, Zúñiga, Luis A, Dranse, Helen J, Rourke, Jillian L, Zabel, Brian A, Butcher, Eugene C, Sinal, Christopher J
• Format: Article
• Language: English
• Subjects: Adipocytes; Adiponectin - metabolism; Adipose tissue; Adipose Tissue, White - metabolism; Adiposity - genetics; Adiposity - physiology; Animals; Appetite; Biological and medical sciences; Blood Glucose; Body fat; Body mass; Body Weight - genetics; CD3 antigen; Chemokines; Cytokines - genetics; Cytokines - metabolism; Data processing; Dendritic cells; Diabetes. Impaired glucose tolerance; Dietary Fats; Differentiation; Eating - genetics; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Energy balance; Energy Balance-Obesity; Energy metabolism; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Food consumption; Fundamental and applied biological sciences. Psychology; G protein-coupled receptors; Gene Expression Regulation - physiology; Glucaric Acid - metabolism; Glucose; Glucose Intolerance - genetics; Glucose Intolerance - metabolism; Glucose metabolism; Glucose tolerance; High fat diet; Homeostasis; In vivo methods and tests; Inflammation; Insulin; Insulin - metabolism; Insulin Resistance; Insulin secretion; Interleukin 6; Leptin - metabolism; Liver; Liver - metabolism; Low fat diet; Lymphocytes; Lymphocytes T; Medical sciences; Metabolism; Mice; Mice, Knockout; mRNA; Natural killer cells; Nutrient deficiency; Obesity; Protein turnover; Receptors; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Skeletal muscle; Tumor necrosis factor- alpha; Vertebrates: endocrinology
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2011-1490

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.