Abstract
Our recent in vivo human studies showed that colonic administration of sodium acetate (SA) resulted in increased circulating acetate levels, which was accompanied by increments in whole-body fat oxidation in overweight-obese men. Since skeletal muscle has a major role in whole-body fat oxidation, we aimed to investigate effects of SA on fat oxidation and underlying mechanisms in human primary skeletal muscle cells (HSkMC). We investigated the dose (0–5 mmol/L) and time (1, 4, 20, and 24 h) effect of SA on complete and incomplete endogenous and exogenous oxidation of 14C-labeled palmitate in HSkMC derived from a lean insulin sensitive male donor. Both physiological (0.1 and 0.25 mmol/L) and supraphysiological (0.5, 1 and 5 mmol/L) concentrations of SA neither increased endogenous nor exogenous fat oxidation over time in HSkMC. In addition, no effect of SA was observed on Thr172-AMPKα phosphorylation. In conclusion, our previously observed in vivo effects of SA on whole-body fat oxidation in men may not be explained via direct effects on HSkMC fat oxidation. Nevertheless, SA-mediated effects on whole-body fat oxidation may be triggered by other mechanisms including gut-derived hormones or may occur in other metabolically active tissues.
Highlights
In the last decades obesity has reached pandemic proportions worldwide [1], indicating the necessity to take action and prevent the development of obesity-related comorbidities
We found a significant increase over time, no differences were observed between sodium acetate (SA) and control treated cells in complete (Figure 1C) and incomplete (Figure 1D) endogenous fat oxidation at each timepoint
We showed that distal colonic infusions of acetate and short-chain fatty acids (SCFA) mixtures increased circulating acetate levels (120 min) in overweight/obese humans [7, 37]
Summary
In the last decades obesity has reached pandemic proportions worldwide [1], indicating the necessity to take action and prevent the development of obesity-related comorbidities. It is increasingly clear that not adipose mass per se but rather adipose tissue dysfunction plays a central role in the observed metabolic derangements [1]. A limited buffering capacity may result in systemic lipid overflow and an increased lipid supply to non-adipose tissues. This may, together with an impaired oxidative capacity cause ectopic fat deposition in important metabolically active tissues (i.e. skeletal muscle, liver), which may link to the development of insulin resistance [2].
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