The Pivotal Role of the Membrane-Bound O-Acyltransferase Domain Containing 7 in Non-Alcoholic Fatty Liver Disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a common and prevalent disorder affecting 25 percent of the adults in the United States and 32 percent of adults globally. It is one of the common causes of chronic liver disease characterized by steatosis, which can lead to inflammation, fibrosis, and cirrhosis. NAFLD is strongly associated with obesity and insulin resistance. Multiple genetic variants have been consistently found to be associated with NAFLD; one of them is found in the TMC4-MBOAT7 loci. One variant (rs641738 C>T) within MBOAT7 encoding lysophosphatidyl inositol acyltransferase increases the risk for NAFLD development and triggers hepatic inflammation by regulating arachidonic acid levels. This review provides an overview of the MBOAT7 gene, pathogenesis of NAFLD, understanding the regulation of MBOAT7 and mechanistic link between MBOAT7 and NAFLD. It further summarizes pathophysiologically relevant in vivo and in vitro studies on MBOAT7 and challenges in treating complex NAFLD with recent progress made in the treatment of NAFLD. As such, this review provides useful information on MBOAT7 and NAFLD interrelation, which has the potential of deciphering novel therapeutic targets rather than well-known genetic variants such as PNPLA3 and TM6SF2.

Effects of Probiotics on Gut Microbiota: An Overview

“…Factors contributing to the pathogenesis of fatty liver disease include adipose tissue dysfunction/inflammation, the dysbiosis of the gut microbiota, and gut barrier function regulating several intrahepatic metabolic and inflammatory pathways. Therefore, probiotics and prebiotics may play a therapeutic role in fatty liver diseases by modulating the gut microbiome [ 115 ]. One study reported that the genetic sequencing of fecal samples from obese patients showed significantly fewer Bacteroidetes and more Firmicutes compared with lean volunteers [ 116 ].…”

The signaling pathways in obesity‐related complications

“…70 Obesity, metabolic syndrome, and dyslipidemia are linked by insulin resistance in peripheral tissues, which leads to an increased hepatic flux of fatty acids from lipolysis and from adipose tissue that is resistant to the anti-lipolytic effects of insulin. 71,72 The hallmark feature of hypertriglyceridemia, due to increased FFA fluxes leads to hepatic accumulation of triglycerides. This, in turn, increases hepatic synthesis of VLDL hampering the lipolysis of chylomicrons and resulting in increased remnant triglycerides transported to the liver.…”

“… 70 Obesity, metabolic syndrome, and dyslipidemia are linked by insulin resistance in peripheral tissues, which leads to an increased hepatic flux of fatty acids from lipolysis and from adipose tissue that is resistant to the anti‐lipolytic effects of insulin. 71 , 72 …”

Perilipins: A family of five fat‐droplet storing proteins that play a significant role in fat homeostasis

“…They store cholesterol esters and contain steroid hormones and triglycerides, which are used as an energy source and precursor for membrane phospholipid synthesis. 1,2 Under normal physiological conditions, hepatic lipid droplets are small and are limited in number. However, excessive hepatic lipid accumulation leads to an increase in the number and size of cytosolic lipid droplets.…”