Consumption of decaffeinated coffee protects against the development of early non-alcoholic steatohepatitis: Role of intestinal barrier function

Abstract

BackgroundNon-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide lacking universally accepted therapies. Studies suggest that coffee consumption is associated with a reduced risk of NAFLD; however, molecular mechanisms and ingredients involved remain to be fully understood. Here, we determined the effects of regular intake of decaffeinated coffee on the development of NAFLD in mice, and molecular mechanisms involved.MethodsFemale C57BL/6J mice (n = 6–7/ group) were pair-fed either a liquid control diet (C) or fat-, fructose- and cholesterol-rich diet (FFC) +/- decaffeinated coffee (DeCaf, 6 g/kg BW) for 4 days or 6 weeks. Indices of liver damage, hepatic inflammation and parameters of insulin resistance and intestinal permeability as well as nitric oxide system were determined.ResultsEarly signs of insulin resistance and non-alcoholic steatohepatitis (NASH) found after 6 weeks of FFC feeding were significantly lower in FFC+DeCaf-fed mice when compared to FFC-fed animals. Moreover, elevation of portal endotoxin levels and loss of tight junction proteins in proximal small intestine found in FFC-fed mice were significantly attenuated in FFC+DeCaf-fed animals. These beneficial effects of DeCaf were associated with a protection against the significant induction of inducible NO-synthase protein levels and 3-nitrotyrosine protein adducts found in proximal small intestine of FFC-fed mice. Similar protective effects of DeCaf were also found in mice fed the FFC diet short-term.ConclusionOur results suggest that protective effects of DeCaf on the development of NAFLD are at least in part related to maintaining intestinal barrier function.

Coffee prevents fatty liver disease induced by a high-fat diet by modulating pathways of the gut–liver axis

“…An improved gut barrier function induced by coffee in the present study could explain the reduced liver steatosis and the lower serum levels of cholesterol and glucose. Moreover, it is in agreement with our previous observation in rats ( 41 ) and with the recent findings of Brandt et al ( 17 ) who found that consumption of decaffeinated coffee in mice fed with a high-fat, -fructose and -cholesterol diet increased intestinal protein expression of zonulin-1 and occludin, reduced bacterial endotoxin concentration in portal blood and mRNA expression of lipopolysaccharide-binding protein in the liver compared with the mice fed with the same diet without coffee. It is well known that HFD is associated with dysbiosis, intestinal mucosa inflammation and a leaky gut condition leading to metabolic endotoxaemia and consequent liver fat accumulation and inflammation ( 42 ) .…”

“…The scientific literature indicates that gut health is implicated in the development and progression of liver diseases and very little recent evidence exists that coffee can modulate some intestinal functions ( 17 ) .…”

Exchanging dietary fat source with extra virgin olive oil does not prevent progression of diet-induced non-alcoholic fatty liver disease and insulin resistance

“…Previous studies of our group have shown that within 6-8 weeks of feeding a BFC, mice develop severe steatosis with early signs of inflammation, which progresses to early steatohepatitis after 13 weeks of feeding [37,38]. In line with our earlier studies, in livers of BFC-fed mice macrovesicular steatosis and inflammatory foci were present (see Fig 2 and Table 3) and NAS as well as hepatic triglyceride levels were significantly higher than those in both control groups (p<0.05 in comparison to both, C-and CO-fed animals and parameters, see Fig 2 and Table 3).…”

Effects of Caffeine and Chlorogenic Acid on Nonalcoholic Steatohepatitis in Mice Induced by Choline-Deficient, L-Amino Acid-Defined, High-Fat Diet

“…The results of this study cannot attribute the inhibitory effects of coffee on NAFLD/NASH to caffeine or CGA, and other ingredients of coffee might exert inhibitory effects. It was recently reported that consumption of decaffeinated coffee protected against the development of early NASH in mice [ 38 ].…”