Abstract
Short chain fatty acids (SCFA), products of microbial fermentation of dietary fiber, exert multiple metabolic effects in cells. Previously, we had demonstrated that soluble fiber influenced fat mass accumulation, gut microbial community structure and SCFA production in pigs. The current study was designed to identify effects of SCFA treatment during adipogenic differentiation of porcine stromovascular cells on lipid metabolism and adipokine expression. Differentiating cells were treated with varying concentrations of butyrate. Results show that butyrate treatment enhanced adipogenesis and lipid accumulation, perhaps through upregulation of glucose uptake and de novo lipogenesis and other mechanisms that include induction of SREBP-1c, C/EBPα/β, GLUT4, LPL, PPARγ, GPAT4, DGAT1 and DGAT2 expression. In addition, butyrate induced adiponectin expression, resulting in activation of downstream target genes, such as AMPK and AKT. Activation of AMPK by butyrate led to phosphorylation of ACC. Although increased ACO gene expression was seen with butyrate treatment, experiments with the peroxisomal fatty acid inhibitor, thioridazine, suggest that butyrate may have an inhibitory effect on peroxisomal fatty acid oxidation. Our studies also provide evidence that butyrate may inhibit lipolysis, perhaps in an FFAR3-dependent manner. Therefore, this study presents a novel paradigm for butyrate action in adipocytes and shows that adipocytes are capable of utilizing butyrate, leading to increased expression of adiponectin for enhanced glucose uptake and improved insulin sensitivity.
Highlights
Metabolic syndrome is a cluster of risk factors which include obesity, insulin resistance or type II diabetes, dyslipidemia, hypertension and cardiovascular disease (CVD) [1]
To investigate chronic effects of short chain fatty acid (SCFA) on markers of lipid metabolism, cells were exposed to different concentrations of acetate, propionate or butyrate throughout differentiation at concentrations ranging from 0 to 1500 μM
Acetate showed no significant effects on these selected gene markers (Fig 1B), propionate significantly increased Fatty acid synthase (FAS) and adiponectin expression at 1500 μM
Summary
Metabolic syndrome is a cluster of risk factors which include obesity, insulin resistance or type II diabetes, dyslipidemia, hypertension and cardiovascular disease (CVD) [1]. Dietary fiber has a potential to counteract metabolic syndrome phenotype, because it has been reported to lead to decreased fat accumulation and increased insulin sensitivity in humans and animals [2, 3]. Butyrate Promotes Differentiation of Porcine Stromovascular Cells gut microbial community structure in the large intestine [2]. We previously demonstrated [3], that soluble fiber, such as inulin, alleviated high fat diet-induced fat mass accumulation and altered gut microbial structure in pigs. Alteration in gut microbial community structure is strongly associated with changes in short chain fatty acid (SCFA) concentrations in the large intestine [3]
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