Abstract
Nonalcoholic fatty liver disease (NAFLD) is the liver manifestation of the complex metabolic derangements associated with obesity. NAFLD is characterized by excessive deposition of fat in the liver (steatosis) and develops when hepatic fatty acid availability from plasma and de novo synthesis exceeds hepatic fatty acid disposal by oxidation and triglyceride export. Hepatic steatosis is therefore the biochemical result of an imbalance between complex pathways of lipid metabolism, and is associated with an array of adverse changes in glucose, fatty acid, and lipoprotein metabolism across all tissues of the body. Intrahepatic triglyceride (IHTG) content is therefore a very good marker (and in some cases may be the cause) of the presence and the degree of multiple-organ metabolic dysfunction. These metabolic abnormalities are likely responsible for many cardiometabolic risk factors associated with NAFLD, such as insulin resistance, type 2 diabetes mellitus, and dyslipidemia. Understanding the factors involved in the pathogenesis and pathophysiology of NAFLD will lead to a better understanding of the mechanisms responsible for the metabolic complications of obesity, and hopefully to the discovery of novel effective treatments for their reversal.
Highlights
Obesity is associated with altered physiological functions in almost all tissues and organ systems of the body
Hepatic steatosis (i.e., nonalcoholic fatty liver disease (NAFLD)) is a common feature of obesity and is associated with a plethora of metabolic abnormalities including: (1) multi-organ insulin resistance, reflected by the inability of insulin to downregulate hepatic glucose production and subcutaneous adipose tissue lipolysis, and to stimulate muscle glucose uptake, (2) increased pancreatic β-cell insulin secretion to compensate for the impaired insulin action, (3) increased intrahepatic fatty acid availability from systemic and nonsystemic sources, and (4) increased hepatic triglyceride export in the form of very low density lipoproteins (VLDL), which leads to various forms of dyslipidemia (Figure 2)
Despite the progress that has occurred in recent years in the understanding much of the pathophysiology of NAFLD, it still remains unclear whether the presence of liver steatosis is a cause or a consequence of metabolic dysfunction
Summary
Obesity is associated with altered physiological functions in almost all tissues and organ systems of the body. (IHTG), i.e., steatosis, which is the hallmark feature of nonalcoholic fatty liver disease (NAFLD). This can progress to nonalcoholic steatohepatitis (NASH) if inflammation is present, with or without fibrosis, and can lead to cirrhosis. Inflammatory markers such as circulating interleukin (IL)-6, can discriminate NAFLD from NASH with high specificity [1]. NAFLD is associated with increased risk for developing insulin resistance, dyslipidemia (high plasma triglyceride and/or low high density lipoprotein-cholesterol concentrations), and hypertension [3], and is an independent predictor of the development of pre-diabetes and type 2 diabetes [4,5,6].
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