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

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.

Non-Alcoholic Steatohepatitis (NASH) and Organokines: What Is Now and What Will Be in the Future

“…Concerning etiology, the primary agents associated with NAFLD and NASH are the presence of insulin resistance (IR), type 2 diabetes (DM2), obesity, and MS. Other endocrine diseases, such as hypothyroidism and polycystic ovary syndrome, can be associated with this condition since they share the fundamental pathophysiological mechanism of NAFLD: IR, obstructive sleep apnea, hypertension, dyslipidemia, changes in the intestinal microbiota, genetic predisposition, menopause, sedentary lifestyle, and excessive consumption of fructose, saturated fatty acids and carbohydrates [ 2 , 11 , 12 ].…”

DRAK2-SRSF6-regulated RNA alternative splicing is a promising therapeutic target in NAFLD/NASH

“…Nowadays, nonalcoholic fatty liver disease (NAFLD) is spreading quickly worldwide, becoming one of the most common chronic liver disorder and affecting one quarter of the world population [ [1] , [2] , [3] ]. NAFLD comprises a disease spectrum ranging from steatosis, which is the accumulation of fat in the liver, to nonalcoholic steatohepatitis (NASH), and finally cirrhosis, which represents the most significant risk factor for hepatocellular carcinoma (HCC) [ 1 , 4 ]. However, due to the complexity and our limited understanding of the pathophysiology of NAFLD, NASH, which represents the advanced stage of NAFLD with serious consequences, currently lacks approved pharmacological therapies.…”

“…However, due to the complexity and our limited understanding of the pathophysiology of NAFLD, NASH, which represents the advanced stage of NAFLD with serious consequences, currently lacks approved pharmacological therapies. Mitochondrial dysfunction and damage induced by overnutrition lead to inflammation, oxidative stress, liver cell death and collagen production, which advance hepatic steatosis to NASH, liver cirrhosis and, potentially, HCC [ 1 ]. Alterations in mRNA splicing constitute significant causal factors of disease, being involved in a plethora of human disorders [ 5 ].…”

Emerging roles for stress kinase p38 and stress hormone fibroblast growth factor 21 in NAFLD development

“…Non-alcoholic fatty liver disease (NAFLD), which is currently the most frequent cause of chronic liver disease worldwide, is characterized by the accumulation of fat in the liver (steatosis) exceeding 5% of total liver's weight, in the absence of significant alcohol consumption [ [1] , [2] , [3] ]. NAFLD is associated with a plethora of metabolic comorbidities such as overweight/obesity, prediabetes, type 2 diabetes mellitus (t2DM), hypertension and dyslipidemia [ [1] , [2] , [3] , [4] ]. NAFLD could also be present in a significant percentage of non-obese subjects [ 1 ].…”

“…NAFLD is associated with a plethora of metabolic comorbidities such as overweight/obesity, prediabetes, type 2 diabetes mellitus (t2DM), hypertension and dyslipidemia [ [1] , [2] , [3] , [4] ]. NAFLD could also be present in a significant percentage of non-obese subjects [ 1 ]. Liver is considered an endocrine organ that modulated systemic lipid homeostasis via the production of hepatokines [ 5 ].…”