The Effects of Butyrate on Induced Metabolic-Associated Fatty Liver Disease in Precision-Cut Liver Slices.
Gerian G H PrinsMelany Rios-MoralesAlbert GerdingDirk-Jan ReijngoudPeter OlingaBarbara M BakkerPublished in: Nutrients (2021)
Metabolic-associated fatty liver disease (MAFLD) starts with hepatic triglyceride accumulation (steatosis) and can progress to more severe stages such as non-alcoholic steatohepatitis (NASH) and even cirrhosis. Butyrate, and butyrate-producing bacteria, have been suggested to reduce liver steatosis directly and systemically by increasing liver β-oxidation. This study aimed to examine the influence of butyrate directly on the liver in an ex vivo induced MAFLD model. To maintain essential intercellular interactions, precision-cut liver slices (PCLSs) were used. These PCLSs were prepared from male C57BL/6J mice and cultured in varying concentrations of fructose, insulin, palmitic acid and oleic acid, to mimic metabolic syndrome. Dose-dependent triglyceride accumulation was measured after 24 and 48 h of incubation with the different medium compositions. PCLSs viability, as indicated by ATP content, was not affected by medium composition or the butyrate concentration used. Under induced steatotic conditions, butyrate did not prevent triglyceride accumulation. Moreover, it lowered the expression of genes encoding for fatty acid oxidation and only increased C4 related carnitines, which indicate butyrate oxidation. Nevertheless, butyrate lowered the fibrotic response of PCLSs, as shown by reduced gene expression of fibronectin, alpha-smooth muscle actin and osteopontin, and protein levels of type I collagen. These results suggest that in the liver, butyrate alone does not increase lipid β-oxidation directly but might aid in the prevention of MAFLD progression to NASH and cirrhosis.
Keyphrases
- gene expression
- fatty acid
- metabolic syndrome
- smooth muscle
- diabetic rats
- high glucose
- hydrogen peroxide
- insulin resistance
- type diabetes
- high fat diet
- drug induced
- high fat diet induced
- adipose tissue
- oxidative stress
- cardiovascular disease
- nitric oxide
- systemic sclerosis
- transcription factor
- weight loss
- amino acid
- early onset
- skeletal muscle
- tissue engineering
- cell migration
- genome wide identification