Intravenous Acetate Elicits a Greater Free Fatty Acid Rebound in Normal than Hyperinsulinaemic Humans

BACKGROUND/OBJECTIVES: Colonic fermentation of dietary fiber may improve insulin sensitivity via the metabolic effects of short chain fatty acids (SCFA) in reducing free fatty acids (FFA). The main objectives of this study were to compare peripheral uptake of acetate (AC) in participants with normal (< 40pmol/L, NI) and high (≥ 40pmol/L, HI) plasma-insulin and the ability of AC to reduce FFA in both groups. SUBJECT/METHODS: Overnight fasted NI (n = 9) and HI (n = 9) participants were given an intravenous (IV) infusion of 140 mmol/L sodium acetate at 3 different rates over 90 minutes. The total amount of AC infused was 51.85 mmols. RESULTS: Acetate clearance in NI participants was not significantly different than that in HI participants (2.11 ± 0.23 vs 2.09 ± 0.24 ml/min). FFA fell in both groups, but rebounded to a greater extent in NI than HI participants (time × group interaction, P = 0.001). Significant correlations between insulin resistance (IR) indices (HOMA-IR, Matsuda and Insulinogenic Index) vs FFA rebound during IV AC infusion were also observed. CONCLUSIONS: These findings suggest that AC uptake is similar in both groups. Participants with lower plasma insulin and lower IR indices had a greater FFA rebound. These results support the hypothesis that increasing AC concentrations in the systemic circulation may reduce lipolysis and plasma FFA concentrations and thus improve insulin sensitivity. More in-depth studies are needed to look at the effects of SCFA on FFA metabolism in insulin resistant participants.