Regulation of key markers of lipid metabolism by short chain fatty acids in differentiated pig adipocytes

Abstract Text: Short chain fatty acids (SCFA), primarily acetate, propionate and butyrate, are the major carbohydrate fermentation end products of in the gut. Previously, we had demonstrated that inulin, a fermentable fiber, alleviated high fat diet induced fat mass accumulation, and that this was accompanied by increased expression of acyl CoA oxidase (ACO), a marker of peroxisomal fatty acid oxidation, decreased expression of fatty acid synthase (FAS) and alteration in the gut microbial community structure to favor increased level of butyrate-producing bacteria. Although gut microbial structure is highly associated with SCFAs production, direct effect of SCFAs on lipid metabolism is still unclear. Therefore, we examined, by RT-PCR, the effect of SCFAs administration on markers of lipid metabolism in differentiated pig adipocytes. Increasing concentrations of SCFAs (µM to low mM) led to an upregulation of expression of acyl CoA oxidase (ACO) and sterol regulatory element binding protein 1c (SREBP-1c), which play a key role in fatty acid synthesis. Furthermore, butyrate, but not propionate and acetate, significantly reduced (P < 0.05) the expression of fatty acids synthase (FAS) and carnitine palmitoyl transferase 1α (CPT1α). Butyrate, but not propionate and acetate, significantly increased (P<0.05) adiponectin and glucose transporter type 4 (GLUT4) expression and led to decreased leptin expression. This study showed that SCFAs, especially butyrate, may exert direct influence on lipid metabolism and adipokine expression profile in adipocytes. Results are consistent with previously observed in vivo effects of fermentable fiber on metabolic markers in pig adipose tissue and suggest that in vivofiber effects may be partly mediated by SCFA produced during fiber fermentation.

Keywords: SCFA adipocyte metabolism