title: 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.
authors.affiliation: Bassett Healthcare , Cooperstown, NY , USA ; Clore Laboratory, University of Buckingham , Buckingham , UK.
authors.forename: John M
authors.initials: JM
authors.lastname: Rumberger
authors.affiliation: Clore Laboratory, University of Buckingham , Buckingham , UK.
authors.forename: Jonathan R S
authors.initials: JR
authors.lastname: Arch
authors.affiliation: Department of Chemistry and Biochemistry, SUNY Oneonta , Oneonta, NY , USA.
authors.forename: Allan
authors.initials: A
authors.lastname: Green
keywords: Adipoctes; Adipose tissue; Butyrate; Histone deacetylase inhibitors; Lipolysis; Short-chain fatty acids