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Obesity is a major risk factor for the development of insulin resistance and type 2 diabetes. Adipose tissue secretes various bioactive molecules, referred to as adipokines, whose dysregulation can mediate changes in glucose homeostasis and inflammatory responses. Here, we identify C1qdc2/CTRP12 as an insulin-sensitizing adipokine that is abundantly expressed by fat tissues and designate this adipokine as adipolin (adipose-derived insulin-sensitizing factor). Adipolin expression in adipose tissue and plasma was reduced in rodent models of obesity. Adipolin expression was also decreased in cultured 3T3-L1 adipocytes by treatment with inducers of endoplasmic reticulum stress and inflammation. Systemic administration of adipolin ameliorated glucose intolerance and insulin resistance in diet-induced obese mice. Adipolin administration also reduced macrophage accumulation and proinflammatory gene expression in the adipose tissue of obese mice. Conditioned medium from adipolin-expressing cells diminished the expression of proinflammatory cytokines in response to stimulation with LPS or TNFα in cultured macrophages. These data suggest that adipolin functions as an anti-inflammatory adipokine that exerts beneficial actions on glucose metabolism. Therefore, adipolin represents a new target molecule for the treatment of insulin resistance and diabetes.
From the Departments of Cardiology and.
This article was published in the following journal.
Name: The Journal of biological chemistry
We investigated the association of the adipokine C1q/TNF-related protein (CTRP) 1 with coronary artery disease (CAD), and the biological vascular effects of CTRP1.
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A protein that has been shown to function as a calcium-regulated transcription factor as well as a substrate for depolarization-activated CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASES. This protein functions to integrate both calcium and cAMP signals.
Cell surface receptors for ADIPOKINES, cytokines secreted by the ADIPOCYTES.
A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia.
A multifunctional protein that is found primarily within membrane-bound organelles. In the ENDOPLASMIC RETICULUM it binds to specific N-linked oligosaccharides found on newly-synthesized proteins and functions as a MOLECULAR CHAPERONE that may play a role in PROTEIN FOLDING or retention and degradation of misfolded proteins. In addition calreticulin is a major storage form for CALCIUM and functions as a calcium-signaling molecule that can regulate intracellular calcium HOMEOSTASIS.
A poly(A) binding protein that has a variety of functions such as mRNA stabilization and protection of RNA from nuclease activity. Although poly(A) binding protein I is considered a major cytoplasmic RNA-binding protein it is also found in the CELL NUCLEUS and may be involved in transport of mRNP particles.
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