Butyrate and other Short-Chain Fatty Acids Increase the Rate of Lipolysis in 3T3-L1 Adipocytes

Abstract

We determined the effect of butyrate and other short-chain fatty acids (SCFA) on rates of lipolysis in 3T3-L1 adipocytes. Prolonged treatment with butyrate (5 mM) increased the rate of lipolysis approximately 2-3-fold. Aminobutyric acid and acetate had little or no effect on lipolysis, however propionate stimulated lipolysis, suggesting that butyrate and propionate act through their shared activity as histone deacetylase (HDAC) inhibitors. Consistent with this, the HDAC inhibitor trichostatin A (1 μM) also stimulated lipolysis to a similar extent as did butyrate. Western blot data suggested that neither mitogen-activated protein kinase (MAPK) activation nor perilipin down-regulation are necessary for SCFA-induced lipolysis. Stimulation of lipolysis with butyrate and trichostatin A was glucose-dependent. Changes in AMP-activated protein kinase (AMPK) phosphorylation mediated by glucose were independent of changes in rates of lipolysis. The glycolytic inhibitor iodoacetate prevented both butyrate- and Tumor necrosis factor-alpha-(TNF-α ) mediated increases in rates of lipolysis indicating glucose metabolism is required. However, unlike TNF-α - , butyrate-stimulated lipolysis was not associated with increased lactate release or inhibited by activation of pyruvate dehydrogenase (PDH) with dichloroacetate. These data demonstrate an important relationship between lipolytic activity and reported HDAC inhibitory activity of butyrate, other short-chain fatty acids and trichostatin A. Given that HDAC inhibitors are presently being evaluated for the treatment of diabetes and other disorders, more work will be essential to determine if these effects on lipolysis are due to inhibition of HDAC.

Low and high concentrations of butyrate regulate fat accumulation in chicken adipocytes via different mechanisms

“…Additionally, TSA can partially mimic the effect of high dose butyrate on fat accumulation. AMPK phosphorylation and the MAPK (mitogen-activated protein kinase) pathway have been reported to be involved in the role of butyrate in fat metabolism in mammals [8][9][10]20]. However, in this study, neither the p-AMPK/AMPK nor the p-ERK/ERK ratio was affected by butyrate at either low or high dose.…”

“…SB ranging from 0.01 to 2 mM were supplemented into cells during the induction period of preadipocytes into mature adipocytes. The concentrations were selected based on previous reports and the physiological ranges [10,12,20]. To detect the phosphorylation status of ERK and AMPK, confluent preadipocytes were treated with 0.01 mM SB or 1 mM SB for 3 min, 5 min, 10 min, 30 min, and 60 min, respectively.…”

Effects of dietary fibres on gut microbial metabolites and liver lipid metabolism in growing pigs

“…Several mechanisms may explain the changes in hepatic lipid content. The butyrate produced in intestinal lumen, which is an energy source for colonocytes, can activate the AMPK signalling pathway in intestinal epithelium, inhibiting hepatic cholesterol and fatty acids synthesis (Gao et al., 2019; Rumberger, Arch, & Green, 2014; Song et al., 2019). In our study, a combined wheat bran fibre and inulin diet feeding tended to reduce the butyrate concentrations in colon, which may lead to a reduced inhibition of hepatic lipid accumulation.…”

Butyrate stimulates adipose lipolysis and mitochondrial oxidative phosphorylation through histone hyperacetylation‐associated β3‐adrenergic receptor activation in high‐fat diet‐induced obese mice

“…Butyrate is a short-chain fatty acid produced through fermentation of dietary fibres in the lower intestinal tract (Pryde et al 2002). Dietary supplementation of butyrate has been shown to prevent high-fat diet-induced obesity in mice (Gao et al 2009) and in 3T3-L1 adipocytes (Rumberger et al 2014). In contrast, butyrate treatment attenuates lipolytic responses in rat primary adipocytes (Heimann et al 2015) and in 3T3-L1 adipocytes co-cultured with macrophages (Ohira et al 2013).…”