Metabolic liver disease of obesity and role of adipose tissue in the pathogenesis of nonalcoholic fatty liver disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized cause of liver-related morbidity and mortality. It can develop secondary to numerous causes but a great majority of NAFLD cases occur in patients who are obese or present with other components of metabolic syndrome (hypertension, dyslipidemia, diabetes). This is called primary NAFLD and insulin resistance plays a key role in its pathogenesis. Obesity is characterized by expanded adipose tissue, which is under a state of chronic inflammation. This disturbs the normal storage and endocrine functions of adipose tissue. In obesity, the secretome (adipokines, cytokines, free fatty acids and other lipid moieties) of fatty tissue is amplified, which through its autocrine, paracrine actions in fat tissue and systemic effects especially in the liver leads to an altered metabolic state with insulin resistance (IR). IR leads to hyperglycemia and reactive hyperinsulinemia, which stimulates lipid-accumulating processes and impairs hepatic lipid metabolism. IR enhances free fatty acid delivery to liver from the adipose tissue storage due to uninhibited lipolysis. These changes result in hepatic abnormal fat accumulation, which may initiate the hepatic IR and further aggravate the altered metabolic state of whole body. Hepatic steatosis can also be explained by the fact that there is enhanced dietary fat delivery and physical inactivity. IR and NAFLD are also seen in various lipodystrophic states in contrary to popular belief that these problems only occur due to excessive adiposity in obesity. Hence, altered physiology of adipose tissue is central to development of IR, metabolic syndrome and NAFLD.

Synergistic effect of fatty liver and smoking on metabolicsyndrome

“…Third, the smoking data was collected by binary criteria in this study so the effects of smoking on metabolic syndrome components might be underestimated [35] . In summary, fatty liver and smoking were closely related to insulin resistance [1][2][3][4][5][6][7][8][9][11][12][13][14]16,[21][22][23]25,32] , and our study provided evidence that fatty liver and smoking had a synergistic effect on metabolic syndrome and its components, especially for triglyceride and HDL-C levels. We suggested that smoking cessation would have the great benefit of reducing the risk of metabolic syndrome, especially for subjects with fatty liver.…”

“…The association between fatty liver and metabolic syndrome was broadly discussed in previous studies [1][2][3][4][5][6][7][8][9] . Fatty liver is often associated with central obesity, type 2 diabetes mellitus, dyslipidemia, and hypertension.…”

Non‐alcoholic fatty liver disease is associated with cardiovascular disease risk markers

“…Besides excessive non-esterified fatty acid influx, mediating factors may include: (i) components of the metabolic syndrome (14,15); (ii) cytokines (16)(17)(18)(19)(20)(21)(22)(23)(24) and (iii) mitochondrial dysfunction (25) (Fig. 1).…”

Increased Secretion and Expression of Myostatin in Skeletal Muscle From Extremely Obese Women

“…Because secreted proteins are also involved in the progression of cardiovascular disease and cancer, there is significant interest in mining the secretome for novel biological markers (5). Whereas endocrine organs specialize in the secretion of proteins into circulation, there is mounting evidence that adipose tissue and skeletal muscle constitutively or intermittently secrete bioactive proteins (6,7). In this study, we hypothesized that skeletal muscle of extremely obese and insulinresistant women would secrete proteins into circulation that act as prognostic or diagnostic biomarkers of obesityassociated comorbidities.…”