Effect of short chain fatty acids on the expression of free fatty acid receptor 2 (Ffar2), Ffar3 and early-stage adipogenesis

Abstract

Adipose tissue has a major influence on insulin sensitivity. Stimulation of free fatty acid receptor 2 (FFAR2) has been proposed to influence adipocyte differentiation. We hypothesised that exposing preadipocytes to short chain fatty acids would induce earlier expression of nuclear receptors that co-ordinate adipogenesis, triglyceride accumulation and leptin secretion. 3T3-L1 preadipocytes were differentiated in the presence of 1 μM acetate, 0.1–10 μM propionate or vehicle control. In experiment 1, expression of Ffar2 and nuclear receptor mRNA was measured by quantitative PCR over 48 h following onset of differentiation. In experiment 2, extracellular leptin concentration and intracellular triglyceride content were measured at days 0, 2, 4, 6, 8 and 10 following the onset of differentiation. Control cells exhibited similar temporal dynamics of gene expression, triglyceride accumulation and leptin secretion as reported previously. We were unable to detect expression of Ffar3 mRNA at any stage of differentiation. Consistent with a lack of Ffar2 expression in the first 24 h of differentiation, acetate and propionate had no significant effect on nuclear receptor expression. Furthermore, acetate or propionate treatment did not alter leptin concentration or triglyceride content. In conclusion, we observed no significant effect of propionate or acetate on adipogenesis in 3T3-L1 cells using validated quantitative techniques.

Short Chain Fatty Acids Prevent High-fat-diet-induced Obesity in Mice by Regulating G Protein-coupled Receptors and Gut Microbiota

“…Some studies reported that the SCFAs, propionate and acetate increase the leptin expression in adipocytes in vitro , whereas butyrate has no effects3031. However, Frost et al failed to demonstrate a significant effect of SCFAs on leptin secretion in adipocytes32. Furthermore, the leptin mRNA expression has been found to be up-regulated by GPR43 activation in some studies or by GPR41 activation in others2930.…”

The role of short chain fatty acids in appetite regulation and energy homeostasis

“… 43 , 46 Zaibi et al 46 suggest that the SCFA-stimulated increase in leptin expression is mediated by FFA2 and that the downregulation of FFA2 in FFA3 KO mice is responsible for the reduction in SCFA-stimulated leptin secretion observed in FFA3 KO mice. However, Frost et al 47 failed to demonstrate a significant effect of SCFAs on leptin secretion in adipocytes.…”

“… 37 , 38 , 42 However, reports investigating the expression of both SCFA receptors in adipose tissue have proven to be inconsistent. 37 , 43 , 45 , 46 , 47 …”

Short-chain fatty acids in control of body weight and insulin sensitivity

“…However, whether these findings extend to human adipocytes, in which both GPR41 and GPR43 are expressed (in contrast to 3T3-L1 adipocytes that only express GPR43) remains to be determined. [126][127][128][129][130] In addition to intracellular (that is, endogenous) lipolysis, extracellular lipolysis mediated by lipoprotein lipase (LPL) might also be affected by SCFA in adipose tissue. Incubation of omental adipose tissue explants from overweight humans with propionate (3 mmol/l for 24 h) resulted in an increased expression of LPL mRNA.…”