Metabolic Targets in Nonalcoholic Fatty Liver Disease

Abstract

This review highlights the major metabolic drivers of nonalcoholic fatty liver disease pathogenesis and gives a current overview of the treatment landscape for nonalcoholic steatohepatitis.

Exosomal miRNAs Profile in Children’s Nonalcoholic Fatty Liver Disease and the Correlation with Transaminase and Uric Acid

“…Dietary, genetic and environmental factors may lead to fat accumulates in the liver, obesity, insulin resistance and changes in the intestinal microbiome. The excessive load of free fatty acid in the liver is the crucial cause of liver steatosis and lipolysis of adipose tissue, de novo lipogenesis and TG dietary input constituted 3 main factors of hepatocyte triacylglycerol deposition [25]. Insulin resistance can increase hepatic denovo lipogenesis and adipose tissue lipolysis [26], and changes of the intestinal microbiome will increase fatty acid absorption [27].…”

Treatment of nonalcoholic fatty liver disease: from adult trials to perspectives in the management of children and adolescents

“…Pioglitazone, another insulin sensitizer, is a thiazolidinedione acting as PPARγ activator, approved for the treatment of T2DM. Contrary to metformin, pioglitazone ameliorates liver histopathology in NASH patients and thus, may be considered for biopsy-proven adult NASH patients according to American and European guidelines [1,6,18]. However, the adverse effect of pioglitazone on weight gain, bone metabolism and a potential minimal effect on bladder cancer should be considered before its treatment initiation [18].…”

“…Another interesting agent is resmetirom (MGL-3196, Madrigal Pharmaceuticals), which is a selective agonist of thyroid hormone receptor in the liver [1]. It binds the main hepatic thyroxine (T4) receptor, leading to increased cholesterol excretion through bile.…”

“…Nonalcoholic fatty liver disease (NAFLD) is associated with the metabolic syndrome (MetS a cluster of interrelated conditions including obesity, hypertension, type 2 diabetes mellitus (T2DM), insulin resistance (IR) and dyslipidemia [1]), is considered the most predominant form of chronic liver disease in childhood/adolescence and its prevalence ranges from 7.6% to 34.2% [2]. Several factors contribute to disease development, supporting, therefore, a multifactorial etiology; obesity, race/ ethnicity (Black non-Hispanic children are less susceptible), genetic influences (e.g.…”

“…Beyond the initially recommended conservative measures with life-style modifications, which often fail to achieve or maintain long term, due to incompliance [1,5,15], the necessity for developing effective medications is urgent. However, there is no specific approved pharmacotherapy for NAFLD in the US, Europe or Asia [6,[16][17][18].…”