Tributyrin Inhibits Ethanol-Induced Epigenetic Repression of CPT-1A and Attenuates Hepatic Steatosis and Injury

Abstract

Healthy Liver or A enuated Steatosis Cons tu ve or Restored CPT-1A expression Suppressed CPT-1A expression Fa y Liver (Steatosis) p300 PGC1 p300 Transcrip onally Permissive Carni ne Palmitoyltransferase-1A (CPT-1A) Promoter Transcrip onally Repressive Carni ne Palmitoyltransferase-1A (CPT-1A

Tributyrin Attenuates Metabolic and Inflammatory Changes Associated with Obesity through a GPR109A-Dependent Mechanism

“…These findings were associated with amelioration of systemic glucose homeostasis (lower fasting glucose, an improved glucose tolerance and higher insulin sensitivity). These protective effects on the liver of obese mice together with the capacity of Tb to attenuate liver steatosis and injury in other experimental models [57][58][59] indicate that this organ is a key target of Tb. Indeed, after Tb administration, high concentrations of butyrate have been observed in the portal vein and liver [58].…”

“…These protective effects on the liver of obese mice together with the capacity of Tb to attenuate liver steatosis and injury in other experimental models [57][58][59] indicate that this organ is a key target of Tb. Indeed, after Tb administration, high concentrations of butyrate have been observed in the portal vein and liver [58]. This SCFA can then act directly on hepatocytes, as demonstrated by a recent study [58], inhibiting histone deacetylases (HDACs) and, consequently, affecting the expression of important genes for hepatic function, such as carnitine palmitoyltransferase-1 (CPT-1A).…”

“…Indeed, after Tb administration, high concentrations of butyrate have been observed in the portal vein and liver [58]. This SCFA can then act directly on hepatocytes, as demonstrated by a recent study [58], inhibiting histone deacetylases (HDACs) and, consequently, affecting the expression of important genes for hepatic function, such as carnitine palmitoyltransferase-1 (CPT-1A). The hepatic beneficial effects of tributyrin/butyrate can also be secondary to its action on other tissues such as the intestine [57] or WAT.…”

Transcriptional signatures of the small intestinal mucosa in response to ethanol in transgenic mice rich in endogenous n3 fatty acids

“…Supplementation with saturated long-chain fatty acids (LCFAs) positively affected EtOH-mediated alterations in the intestinal barrier and gut microbiota dysbiosis 11 . It has been shown that tributyrin, a triglyceride found in butter and margarine, prevents alcohol-induced tight-junction (TJ) disruption, which in turn protects against intestinal hyperpermeability 12 . Various dietary fatty acids also differentially modulate EtOH-induced changes in the gut microbiome.…”

Targeting Epigenetic Mechanisms to Alleviate Alcoholic Steatosis

“…In this issue of Cellular and Molecular Gastroenterology and Hepatology, building on their own group's earlier reports, Donde et al 6 present novel findings that chronic alcohol induces histone Histone H3 Lysine 9 (H3K9) deacetylation in the promoter region of the fatty acid oxidation gene, carnitine palmitoyltransferase-1A (CPT-1A), indicating a closed or repressive chromatin state and hence reduced CPT-1A gene expression in alcoholic steatotic livers.…”