The Role of Visceral Adipose Tissue in the Pathogenesis of Non-alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD), the most common cause of chronic liver disease in Western countries, comprises a disease spectrum ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), advanced fibrosis and cirrhosis. Fatty liver develops when fatty acid uptake and de novo fatty acid synthesis exceed fatty acid oxidation and export as very low-density lipoprotein/triglycerides. Because of its high prevalence and its association with obesity, metabolic syndrome, type 2 diabetes, dyslipidaemia and hypertension, NAFLD has become an important public health problem. The pathogenesis of NAFLD has to date not been completely clarified. Research has been conducted regarding the role of insulin resistance, lipotoxicity, oxidative stress and chronic inflammation. Visceral adipose tissue has increasingly been recognised as a biologically active organ contributing to the pathogenesis of NAFLD. Its role in the development of fatty liver might be situated at several levels: as a source of free fatty acids, by the production of adipocytokines, as a cause of insulin resistance and by inflammation.

Download Full-text

Non-Alcoholic Fatty Liver Disease: From Pathogenesis to Clinical Impact

Processes ◽

10.3390/pr9010135 ◽

2021 ◽

Vol 9 (1) ◽

pp. 135

Author(s):

Alfredo Caturano ◽

Carlo Acierno ◽

Riccardo Nevola ◽

Pia Clara Pafundi ◽

Raffaele Galiero ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Clinical Impact ◽

Alcoholic Fatty Liver ◽

Adipose Tissue Lipolysis ◽

Visceral Adipose ◽

Alcoholic Fatty Liver Disease

Non-Alcoholic Fatty Liver Disease (NAFLD) is caused by the accumulation of fat in over 5% of hepatocytes in the absence of alcohol consumption. NAFLD is considered the hepatic manifestation of metabolic syndrome (MS). Recently, an expert consensus suggested as more appropriate the term MAFLD (metabolic-associated fatty liver disease). Insulin resistance (IR) plays a key role in the development of NAFLD, as it causes an increase in hepatic lipogenesis and an inhibition of adipose tissue lipolysis. Beyond the imbalance of adipokine levels, the increase in the mass of visceral adipose tissue also determines an increase in free fatty acid (FFA) levels. In turn, an excess of FFA is able to determine IR through the inhibition of the post-receptor insulin signal. Adipocytes secrete chemokines, which are able to enroll macrophages inside the adipose tissue, responsible, in turn, for the increased levels of TNF-α. The latter, as well as resistin and other pro-inflammatory cytokines such as IL-6, enhances insulin resistance and correlates with endothelial dysfunction and an increased cardiovascular (CV) risk. In this review, the role of diet, intestinal microbiota, genetic and epigenetic factors, low-degree chronic systemic inflammation, mitochondrial dysfunction, and endoplasmic reticulum stress on NAFLD have been addressed. Finally, the clinical impact of NAFLD on cardiovascular and renal outcomes, and its direct link with type 2 diabetes have been discussed.

Download Full-text