Obesity, characterized by an excess of adipose tissue, is an established risk factor
for cardiovascular disease and type II diabetes. Different mechanisms linking obesity with
these comorbidities have been postulated but remain poorly understood. Adipose tissue
secretes bioactive signaling molecules, termed adipokines, which regulate various
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). Herein, we have shown that serum levels of the novel adipokine
chemerin are significantly elevated in mouse models of obesity/diabetes. Administration
of exogenous chemerin exacerbates glucose intolerance, lowers serum insulin levels, and
decreases tissue glucose uptake in obese/diabetic but not normoglycemic mice. In
CMKLR1-deficient mice food consumption, total body mass, and percent body fat are
lower compared to wildtype controls, regardless of diet (low or high fat). CMKLR1-/-
mice also exhibited decreased hepatic and white adipose tissue TNF? 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 also
glucose intolerant compared to wildtype 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
chemerin/CMKLR1 signaling influences adipose tissue development, inflammation, and
glucose homeostasis and may contribute to the metabolic derangements characteristic of
obesity and obesity-related diseases.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:NSHD.ca#10222/14305 |
| Date | 14 October 2011 |
| Creators | Ernst, Matthew |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | en_US |
| Detected Language | English |
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