Effects of Short Chain Fatty Acids on Glucose and Lipid metabolism in Adipocytes

Abstract

Short chain fatty acids (SCFA) are major products of bacterial fermentation by gut microbiota. Recent literature suggests that microbiota contribute to regulate glucose homeostasis and insulin sensitivity in the host. The purpose of the study was to determine whether the SCFAs acetate, butyrate and propionate impact on glucose and lipid metabolism and insulin signalling in adipose cells in vitro. We cultured differentiated 3T3L1 adipocytes in the presence of acetate, butyrate or propionate for 48 hours. We determined glucose transporter expression and activation of insulin signalling cascades by western blotting. We measured insulin‐stimulated 2‐deoxyglucose uptake and determined total Triglyceride content and expression and activation of Hormone Sensitive lipase (HSL) and Adipose Triglyceride Lipase (ATGL) by western blotting. None of the SCFAs had an effect on Glut1 or Glut4 glucose transporter expression or elicited an effect on basal or insulin‐stimulated glucose uptake. Insulin‐mediated activation of AKT and ERK were similar to that obtained in control untreated cells. While acetate and propionate did not have any effect in total triglyceride accumulation compared to control cells, butyrate treated cells showed lower lipid content compared to untreated cells. Butyrate treated cells showed increased levels of phosphorylated HSL (Ser 660) in basal state (no insulin) whereas the response to insulin was similar to that of untreated cells. We did not detect any changes in the expression levels of HSL, but cells treated with butyrate had increased ATGL levels compared to untreated cells. These data suggests that SCFA do not directly modify glucose uptake, and that butyrate but not other SCFA reduces lipid content by increasing the basal activity of HSL and expression of ATGL in adipocytes.