Nonalcoholic fatty liver disease (NAFLD) is a pathology that contains a broad liver dysfunctions spectrum. These alterations span from noninflammatory isolated steatosis until nonalcoholic steatohepatitis (NASH), a more aggressive form of the disease characterized by steatosis, inflammatory status, and varying liver degrees fibrosis. NAFLD is the most prevalent chronic liver disease worldwide. The causes of NAFLD are diverse and include genetic and environmental factors. The presence of NASH is strongly associated with cirrhosis development and hepatocellular carcinoma, two conditions that require liver transplantation. The liver alterations during NAFLD are well described. Interestingly, this pathological condition also affects other critical tissues and organs, such as skeletal muscle and even the cardiovascular, renal, and nervous systems. Oxidative stress (OS) is a harmful state present in several chronic diseases, such as NAFLD. The purpose of this review is to describe hepatic and extrahepatic dysfunctions in NAFLD. We will also review the influence of OS on the physiopathological events that affect the critical function of the liver and peripheral tissues.
Skeletal muscle atrophy is characterized by the degradation of myofibrillar proteins, such as myosin heavy chain or troponin. An increase in the expression of two muscle-specific E3 ligases, atrogin-1 and MuRF-1, and oxidative stress are involved in muscle atrophy. Patients with chronic liver diseases (CLD) develop muscle wasting. Several bile acids increase in plasma during cholestatic CLD, among them, cholic acid (CA) and deoxycholic acid (DCA). The receptor for bile acids, TGR5, is expressed in healthy skeletal muscles. TGR5 is involved in the regulation of muscle differentiation and metabolic changes. In this paper, we evaluated the participation of DCA and CA in the generation of an atrophic condition in myotubes and isolated fibers from the muscle extracted from wild-type (WT) and TGR5-deficient (TGR5 −/−) male mice. The results show that DCA and CA induce a decrease in diameter, and myosin heavy chain (MHC) protein levels, two typical atrophic features in C 2 C 12 myotubes. We also observed similar results when INT-777 agonists activated the TGR5 receptor. To evaluate the participation of TGR5 in muscle atrophy induced by DCA and CA, we used a culture of muscle fiber isolated from WT and TGR5 −/− mice.
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