Obesity, fatty liver disease and intestinal microbiota

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disorder that is increasing in prevalence with the worldwide epidemic of obesity. NAFLD is the hepatic manifestation of the metabolic syndrome. The term NAFLD describes a spectrum of liver pathology ranges from simple steatosis to steatosis with inflammation nonalcoholic steatohepatitis and even cirrhosis. Metabolic syndrome and NAFLD also predict hepatocellular carcinoma. Many genetic and environmental factors have been suggested to contribute to the development of obesity and NAFLD, but the exact mechanisms are not known. Intestinal ecosystem contains trillions of microorganisms including bacteria, Archaea, yeasts and viruses. Several studies support the relationship between the intestinal microbial changes and obesity and also its complications, including insulin resistance and NAFLD. Given that the gut and liver are connected by the portal venous system, it makes the liver more vulnerable to translocation of bacteria, bacterial products, endotoxins or secreted cytokines. Altered intestinal microbiota (dysbiosis) may stimulate hepatic fat deposition through several mechanisms: regulation of gut permeability, increasing low-grade inflammation, modulation of dietary choline metabolism, regulation of bile acid metabolism and producing endogenous ethanol. Regulation of intestinal microbial ecosystem by diet modifications or by using probiotics and prebiotics as a treatment for obesity and its complications might be the issue of further investigations.

Keywords: Dysbiosis, Nonalcoholic fatty liver disease; Intestinal microbiota; Obesity.

Figure 1

Some gastrointestinal and systemic conditions related with altered intestinal microbiota[31,32,35].

Figure 2

Effects of gut microbiota on the development of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis through the gut-liver axis. Altered intestinal bacterial composition (dysbiosis) results in degradation of carbohydrates in the intestinal lumen and produces short-chain fatty acids (SCFAs), which are substrates for hepatic lipogenesis and gluconeogenesis. The interaction of SCFAs with G-protein coupled receptors (GPRs) releases the peptide YY (PYY), which modulates gut motility and nutrient absorption. SCFAs stimulate hepatic carbohydrate response element binding protein (ChREBP) and increase lipogenesis. Bacterial translocation to the portal circulation causes interaction of bacterial endotoxins (lipopolysaccharides, LPS) with hepatic toll-like receptors (TLR4 and TLR9) and results in the release of cytokines and chemokines. Decreased Fiaf (fasting-induced adipose factor) levels enhance lipoprotein lipase (LPL) activity and cause fat accumulation. Choline deficiency causes liver steatosis via decreased secretion of very- low-density-lipoprotein-(VLDL) from the liver.

Figure 3

Probable mechanisms of action of the antiobesity effects of modulated intestinal microbiota. CLA: Conjugated linoleic acid; Fiaf: Fasting-induced adipocyte factor.