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. 2021 Nov 16:12:100149.
doi: 10.1016/j.metop.2021.100149. eCollection 2021 Dec.

Metabolic causes and consequences of nonalcoholic fatty liver disease (NAFLD)

Paria Zarghamravanbakhsh  1 , Michael Frenkel  2 , Leonid Poretsky  1   2
Affiliations

Metabolic causes and consequences of nonalcoholic fatty liver disease (NAFLD)

Paria Zarghamravanbakhsh et al. Metabol Open. .

Erratum in

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a multifactorial metabolic disorder that was first described in 1980. It has been prevalent and on the rise for many years and is associated with other metabolic disorders such as obesity and type 2 diabetes mellitus (T2DM). NAFLD can be best described as a metabolic dysfunction that stems from insulin resistance-induced hepatic lipogenesis. This lipogenesis increases oxidative stress and hepatic inflammation and is often potentiated by genetic and gut microbiome dysfunction. As NAFLD progresses from simple steatosis to non-alcoholic steatohepatitis (NASH) and to cirrhosis and hepatocellular carcinoma (HCC), the odds of complications including cardiovascular disease (CVD), chronic kidney disease (CKD), and overall mortality increase. The aim of this review is to describe the metabolic causes and consequences of NAFLD while examining the risks that each stage of NAFLD poses. In this review, the etiology of "lean" NAFLD, the impact of obesity, T2DM, genetics, and microbiome dysbiosis on NAFLD progression are all explored. This review will also discuss the core issue behind the progression of NAFLD: insulin resistance (IR). Upon describing the causes and consequences of NAFLD, the effectiveness of diet modification, lifestyle changes, and glucagon-like peptide 1 receptor (GLP-1) agonists to retard NAFLD progression and stem the rate of complications is examined.

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Figures

Fig. 1
Fig. 1
NAFLD (non-alcoholic fatty liver disease) stems from a combination of genetics, diet, and lifestyle, which drives dysbiosis and other metabolic malfunction. The result is insulin resistance (IR) that drives NAFLD progression. As NAFLD progresses to NASH (non-alcoholic steatohepatitis) and HCC (hepatocellular carcinoma), IR progresses as well and contributes to the development of ASCVD (atherosclerotic cardiovascular disease), PCOS (polycystic ovary syndrome), T2DM (type 2 diabetes-mellitus), and CKD (chronic kidney disease).
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