CXCL12 (stromal cell derived factor-1) secretion by preadipocytes is enhanced by short-chain fatty acids acting through a G protein-coupled receptor (GPR41)
Kennedy, R.L., Thomas, L., Garland, S., and Kazi, M. (2007) CXCL12 (stromal cell derived factor-1) secretion by preadipocytes is enhanced by short-chain fatty acids acting through a G protein-coupled receptor (GPR41). In: Papers from ESA Annual Scientific Meeting 2007, - . From: ESA Annual Scientific Meeting 2007, 2-5 September 2007, Christchurch, New Zealand.
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CXCLl2 is involved in diabetic retinopathy, and decreased secretion in diabetes contributes to defective vascular progenitor cell mobilisation, leading to macrovascular complications. Adipocytes could be an important source of CXCLl2 and other chemokines. The SCF A butyrate stimulates, while other histone deacetylase (HDAC) inhibitors (valproate and trichostatin) inhibit, adipogenesis. 3T3-Ll cells were grown to confluence and studied as preadipocytes or differentiated adipocytes. Butyrate increased CXCLl2 mRNA 5-fold (p < 0.001) and protein secretion 2-fold (p < 0.001) in preadipocytes. CXCLl2 was expressed in adipocytes, but butyrate had modest effects on gene expression and did not affect protein secretion.
CXCLl2 mRNA and protein were not increased in preadipocytes by octanoate or by valproate or trichostatin. SCFAs increased CXCLl2 secretion in preadipocytes, with potency propionate > butyrate > acetate consistent with action through the GPR 41. Pertussis toxin (5 ng/ml), which inhibits receptor-G protein interaction, was without effect alone but abolished the stimulatory effect of SCFA on CXCLl2 expression. SCFA did not affect VEGF mRNA, but decreased VEGF secretion in preadipocytes. In adipocytes, butyrate increased VEGF mRNA and protein (41% and 22%, p < 0.01 and P < 0.05, respectively) whereas HDAC inhibitors decreased VEGF secretion. Hypoxia increased VEGF mRNA (p < 0.001), but decreased CXCLl2 (p < 0.001). MCP-1 was predominantly expressed in preadipocytes, and up-regulated by SCFA (p < 0.001). mRNA for CXCR4, the receptor for CXCLl2 was not detected in preadipocytes or adipocytes, but was present in monocytic cells. GPR41 mRNA was detected in preadipocytes and adipocytes. GPR43, the other known SCFA receptor, was only present in adipocytes.
CXCLl2 may mediate interaction of adipocytes with immune and vascular cells, Regulation by SCFA and hypoxia differs to that of VEGF. Increased preadipocyte differentiation in obesity may contribute to decreased CXCLl2 and this may be partly reversed by functional foods which increase SCF A.
|Item Type:||Conference Item (Poster)|
|Date Deposited:||05 Oct 2010 04:46|
|FoR Codes:||11 MEDICAL AND HEALTH SCIENCES > 1199 Other Medical and Health Sciences > 119999 Medical and Health Sciences not elsewhere classified @ 100%|
|SEO Codes:||92 HEALTH > 9299 Other Health > 929999 Health not elsewhere classified @ 100%|
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