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

Author(s):  
John M. Rumberger ◽  
Jonathan R.S. Arch ◽  
Allan Green

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.

2014 ◽  
Author(s):  
John M. Rumberger ◽  
Jonathan R.S. Arch ◽  
Allan Green

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.


ISRN Allergy ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Paul V. Licciardi ◽  
Katherine Ververis ◽  
Tom C. Karagiannis

Changes in diet can also have dramatic effects on the composition of gut microbiota. Commensal bacteria of the gastrointestinal tract are critical regulators of health and disease by protecting against pathogen encounter whilst also maintaining immune tolerance to certain allergens. Moreover, consumption of fibre and vegetables typical of a non-Western diet generates substantial quantities of short-chain fatty acids (SCFAs) which have potent anti-inflammatory properties. Dietary interventions such as probiotic supplementation have been investigated for their pleiotropic effects on microbiota composition and immune function. Probiotics may restore intestinal dysbiosis and improve clinical disease through elevated SCFA levels in the intestine. Although the precise mechanisms by which such dietary factors mediate these effects, SCFA metabolites such as butyrate also function as histone deacetylase inhibitors (HDACi), that can act on the epigenome through chromatin remodeling changes. The aim of this review is to provide an overview of HDAC enzymes and to discuss the biological effects of HDACi. Further, we discuss the important relationship between diet and the balance between health and disease and how novel dietary interventions such as probiotics could be alternative approach for the prevention and/or treatment of chronic inflammatory disease through modulation of the intestinal microbiome.


2015 ◽  
Vol 15 (2) ◽  
pp. 419-431
Author(s):  
Mohamed Mohamed Soliman ◽  
Tamer Ahmed Ismail ◽  
Ahmed Abdel-Khalik Mansour

Abstract Haptoglobin (Hp) is a protein secreted mainly from the liver to bind hemoglobin and thus prevents iron loss and oxidative stress. Bovine Hp in blood increases during diseases such as mastitis and fatty liver syndrome. This study was conducted to examine the expression and regulation of Hp in differentiated mature bovine adipocytes. Hp expression was confirmed in various tissues and in mature adipocytes but not in the stromal vascular cell fraction using qualitative RT -PCR and quantitative northern blot analysis, respectively. Intravenous injection of Holstein cows with recombinant bovine tumor necrosis factor-α (rbTNF-α) and interferon gamma (rbIFN-γ) significantly increased the serum concentrations of Hp. When mature differentiated bovine adipocytes were incubated with short chain fatty acids, cytokines and hormones, Hp expression was altered. Acetate, butyrate and propionate at a dose of 1 mM significantly up-regulated Hp mRNA abundance. Lipopolysaccharide (LPS) and TNF-α also significantly up-regulated Hp mRNA abundance, while troglitazone and norepinephrine down-regulated it. Our study confirmed expression of Hp in differentiated mature adipocytes and identified LPS, TNF-α, short chain fatty acids, as regulators of Hp mRNA expression in these cells.


2020 ◽  
Vol 9 (9) ◽  
pp. 2764
Author(s):  
Aaron L. Magno ◽  
Lakshini Y. Herat ◽  
Márcio G. Kiuchi ◽  
Markus P. Schlaich ◽  
Natalie C. Ward ◽  
...  

Studying the role of circulatory factors in the pathogenesis of diseases has been key to the development of effective therapies. We sought to examine the effect of antihypertensive therapies on numerous circulatory factors including short chain fatty acids and growth factors in a human cohort. A subset of participants from an earlier study was characterized by their hypertensive and/or treatment status and separated into three groups: (i) normotensives; (ii) untreated hypertensive and (iii) treated hypertensive subjects. Circulating levels of short chain fatty acids, FGF21 and TNF superfamily members were measured as part of this study. Both F2-isoprostane and circulating lipid levels were reanalysed as part of this current study. We found that antihypertensive treatment increased butyrate levels and decreased acetate levels to levels similar to normotensives. We also found that antihypertensive treatments reduced levels of circulating FGF21, TNFSF14 and TNF-α. In conclusion, we identified several circulatory factors that are altered in hypertension.


2019 ◽  
Vol 38 (3) ◽  
pp. 1373-1381 ◽  
Author(s):  
Maša Primec ◽  
Martina Klemenak ◽  
Diana Di Gioia ◽  
Irene Aloisio ◽  
Nicole Bozzi Cionci ◽  
...  

Author(s):  
Alexander Visekruna ◽  
Maik Luu

During the past decade, researchers have investigated the role of microbiota in health and disease. Recent findings support the hypothesis that commensal bacteria and in particular microbiota-derived metabolites have an impact on development of inflammation and carcinogenesis. Major classes of microbial-derived molecules such as short-chain fatty acids (SCFA) and secondary bile acids (BAs) were shown to have immunomodulatory potential in various autoimmune, inflammatory as well as cancerous disease models and are dependent on diet-derived substrates. The versatile mechanisms underlying both beneficial and detrimental effects of bacterial metabolites comprise diverse regulatory pathways in lymphocytes and non-immune cells including changes in the signaling, metabolic and epigenetic status of these. Consequently, SCFAs as strong modulators of immunometabolism and histone deacetylase (HDAC) inhibitors have been investigated as therapeutic agents attenuating inflammatory and autoimmune disorders. Moreover, BAs were shown to modulate the microbial composition, adaptive and innate immune response. In this review, we will discuss the recent findings in the field of microbiota-derived metabolites, especially with respect to the molecular and cellular mechanisms of SCFA and BA biology in the context of intestinal and liver diseases.


1994 ◽  
Vol 92 (4) ◽  
pp. 629-635 ◽  
Author(s):  
Mercedes Gallardo ◽  
Paloma Munoz De Rueda ◽  
Angel Jesus Matilla ◽  
Isabel Maria Sanchez-Calle

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