Short-chain fatty acids increase expression and secretion of stromal cell-derived factor-1 in mouse and human re-adipocytes

Vangaveti, Venkat, Rush, Catherine, Thomas, Linda, Rasalam, Roy R., Malabu, Usman H., McCoombe, Scott G., and Kennedy, Richard L. (2014) Short-chain fatty acids increase expression and secretion of stromal cell-derived factor-1 in mouse and human re-adipocytes. Hormones, 13 (4). pp. 532-542.

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Objective: Stromal cell-derived factor-1 (SDF-1) is expressed in pre-adipocytes but its role is unknown. We investigated butyrate (a histone deacetylase inhibitor - HDACi) and other short-chain fatty acids (SCFA) in the regulation of SDF-1. We further investigated whether effects of SCFA were signalled through G protein-coupled receptors FFA2 and FFA3.

Design and Results: SDF-1 mRNA expression and protein secretion were studied in 3T3-L1 cells and human pre-adipocytes. SDF-1 was abundant, with mRNA and protein levels increased by butyrate. This was replicated with acetate and propionate, but not by trichostatin or valproate. Trichostatin inhibited SDF-1 secretion. Pertussis toxin blocked stimulation by butyrate. The order of potency of SCFA in stimulating SDF-1 (C3 > C4 > C2) is consistent with action through FFA3. Silencing the FFA3 gene abolished butyrate-stimulated SDF-1 expression and secretion. FFA3 was expressed in both pre-adipocytes and adipocytes, while FFA2 was expressed in adipocytes only. SDF-1 expression was low in murine macrophage J774.2 cells, while the SDF-1 receptor CXCR4 was absent from 3T3-L1 cells but abundant in J774.2 macrophages. In human pre-adipocytes, FFA3 was also expressed and SCFA increased SDF-1 secretion.

Conclusions: SDF-1 and CXCR4 may mediate the interaction between adipose stromal cells and macrophages. Effects of SCFA are mediated through FFA3, but not histone deacetylase inhibition.

Item ID: 35378
Item Type: Article (Research - C1)
ISSN: 1109-3099
Keywords: butyrate, fatty acids, FFA2, FFA3, pre-adipocytes, propionate
Funders: James Cook University (JCU), Townsville Hospital Private Practice Fund
Date Deposited: 24 Sep 2014 00:02
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1101 Medical Biochemistry and Metabolomics > 110104 Medical Biochemistry: Lipids @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110306 Endocrinology @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920106 Endocrine Organs and Diseases (excl. Diabetes) @ 50%
92 HEALTH > 9299 Other Health > 929999 Health not elsewhere classified @ 50%
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