Chemerin exacerbates glucose intolerance in mouse models of obesity and diabetes.
Obesity, characterized by an excess of adipose tissue, is an established risk factor for cardiovascular disease and type 2 diabetes. Different mechanisms linking obesity with these comorbidities have been postulated but remain poorly understood. Adipose tissue secretes a number of hormone-like compounds, termed adipokines, that are important for the maintenance of normal glucose metabolism. Alterations in the secretion of adipokines with obesity are believed to contribute to the undesirable changes in glucose metabolism that ultimately result in the development of type 2 diabetes. In the present study, we have shown that serum levels of the novel adipokine chemerin are significantly elevated in mouse models of obesity/diabetes. The expression of chemerin and its receptors, chemokine-like receptor 1, chemokine (C-C motif) receptor-like 2, and G protein-coupled receptor 1 are altered in white adipose, skeletal muscle, and liver tissue of obese/diabetic mice. Administration of exogenous chemerin exacerbates glucose intolerance, lowers serum insulin levels, and decreases tissue glucose uptake in obese/diabetic but not normoglycemic mice. Collectively, these data indicate that chemerin influences glucose homeostasis and may contribute to the metabolic derangements characteristic of obesity and type 2 diabetes.
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
Matthew C
MC
Ernst
Mark
M
Issa
Kerry B
KB
Goralski
Christopher J
CJ
Sinal
D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D018925:Chemokines; D002630:Chemotactic Factors / Q000097:blood* / Q000235:genetics / Q000494:pharmacology; D003920:Diabetes Mellitus / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism / Q000493:pharmacokinetics; D018149:Glucose Intolerance / Q000097:blood* / Q000378:metabolism; D007328:Insulin / Q000097:blood; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood* / Q000235:genetics / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000097:blood* / Q000209:etiology; D054388:Receptors, CCR; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
C486456:CMKLR1 protein, mouse; C111851:Ccrl2 protein, mouse; D018925:Chemokines; D002630:Chemotactic Factors; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D054388:Receptors, CCR; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; C523686:chemerin protein, mouse; D005947:Glucose