Regulation of adipolin/CTRP12 cleavage by obesity.
Summary of "Regulation of adipolin/CTRP12 cleavage by obesity."
Obesity is highly associated with the development of insulin resistance and type 2 diabetes. Recently we found that adipolin/CRTP12 is an adipocytokine that exerts beneficial actions on glucose metabolism. Here we investigated the regulation of circulating adipolin under conditions of obesity and assessed its potential mechanisms. Both full and cleaved forms of adipolin were observed in mouse plasma. Diet-induced obese (DIO) mice showed a significant reduction of plasma levels of full and total (full and cleaved) adipolin compared with control mice, resulting in an increase in the ratio of cleaved to full isoform. In vitro gene transfection studies using HEK293 cells revealed that a deletion mutant of adipolin gene (Δaa90-93) caused a reduction of cleaved production of adipolin in media. A bioinformatics analysis of adipolin amino acid sequence indicated the potential involvement of the family of proprotein convertases (PCs) in cleavage of adipolin. Treatment of 3T3-L1 adipocytes with an inhibitor for PCs abolished the expression of cleaved adipolin form in the media. The expression of furin, the member of PCs, was increased in adipose tissue of DIO mice. Furin expression was also increased in cultured adipocytes by treatment with an inducer of inflammation. These data suggest that obesity states facilitate the cleavage of adipolin presumably through upregulation of furin in adipose tissue.
Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
This article was published in the following journal.
Name: Biochemical and biophysical research communications
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/23068097
- DOI: http://dx.doi.org/10.1016/j.bbrc.2012.10.031
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Medical and Biotech [MESH] Definitions
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A RNA-binding protein that stimulates the cleavage of the 3' end of MRNA near the POLYADENYLATION site. It is a heterotrimer of 55-, 64- and 77-kDa subunits and combines with CLEAVAGE STIMULATION FACTOR to form a stable complex with mRNA that directs the 3' cleavage and polyadenylation reaction.
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An RNA-binding protein that recognizes the AAUAAA RNA SEQUENCE at the 3' end of MRNA. It contains four subunits of 30, 73, 100 and 160 kDa molecular size and combines with CLEAVAGE STIMULATION FACTOR to form a stable complex with mRNA that directs the 3' cleavage and polyadenylation reaction.