Pathogenesis of Hepatic Steatosis and Fibrosis: Role of Leptin

Abstract

Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver abnormalities, ranging from simple steatosis, to steatohepatitis and cirrhosis, in the absence of "excessive" alcohol consumption or any other identifi able cause(s) for liver disease [ 1 ]. Histologically, NAFLD can be categorized into: (1) simple steatosis in the absence of hepatocellular injury (nonalcoholic fatty liver, NAFL); and (2) steatohepatitis (nonalcoholic steatohepatitis, NASH), characterized by the presence of steatosis and infl ammation with hepatic injury (ballooning), with or without fi brosis [ 1 ]. NASH can progress to cirrhosis, liver failure, and rarely liver cancer, whereas the progression to more severe forms of liver disease is minimal in patients with NAFL. Steatosis is the hallmark of NAFL and NAFLD and can be defi ned chemically, when intrahepatic triglyceride (IHTG) content exceeds 5 % of liver volume or liver weight [ 2 ], histologically, when 5 % of hepatocytes contain visible intracellular triglyceride [ 3 ], and radiologically, by using magnetic resonance spectroscopy (MRS) [ 4 ]. The results from one study in subjects who were considered to be at low-risk for NAFLD (i.e., normal weight, normal fasting serum glucose and alanine aminotransferase concentrations, and absence of diabetes) indicate an upper "normal" amount of IHTG of 5.6 % of liver volume, which represented the 95th percentile in this population [ 5 ]. Data from another study found the 95th percentile for IHTG content was 3 % in young lean subjects with normal oral glucose tolerance [ 6 ].NAFLD has become an important public health problem, because of its high prevalence, the potential progression to severe liver disease and its association with serious cardiometabolic abnormalities, such as insulin resistance, type 2 diabetes, and dyslipidemia. The prevalence rate of NAFLD increases with increasing body mass index (BMI) [ 7 ] and varies widely based on the population studied and on the tool used to make the diagnosis. An analysis of liver histology from potential liver donors [ 8 , 9 ], automobile crash victims [ 10 ], autopsy fi ndings [ 11 ], and clinical liver biopsies [ 12 ] suggests that the prevalence of steatosis and steatohepatitis are approximately 15 % and 3 %, respectively, in non-obese individuals, 65 % and 20 %, respectively, in persons

Estimation of Serum and Ascitic Fluid Leptin Levels in Chronic Liver Disease

“…-S61- [17] . As a result of synergistic action of other adipocytokines such as tumor necrosis factor (TNF-α ) , fatty liver may progress to steatohepatitis by lipoapoptosis induction , which leads to the recruitment of inflammatory cells , contributing to its progression and subsequently causing hepatocellular damage , such as cell swelling and appearance of Mallory bodies (Magkos F) [18] .Leptin has proven to be important in the progression of hepatic steatosis (Magkos F) [19] . Our study showed significantly higher ascitic fluid leptin level compared to serum in our patient in both group I, II .…”

Leptin Levels and its Relationship to Liver Dysfunctional Diseases and Hepatocellular Carcinoma

“…These factors include genetic, environmental and psychological conditions. Abdominal obesity (central obesity) is strongly related to Non-Alcoholic Fatty Liver Disease (NAFLD) and Insulin Resistance (IR), mainly because of the excessive body fat in the central region [5,17,25 ] . These conditions lead to a series of complications due to systemic arterial hypertension, dyslipidemia, and inflammation, which are present in metabolic syndrome (MS).…”

“…Two sequential events act as important mechanisms in the establishment and progression of hepatic steatosis: i) continual fatty acids accumulation in hepatocytes and ii) increase of hepatic oxidative stress [56]. The action of oxidative stress is due to the overload of accumulated liver lipids, resulting in oxidation of these compounds of fatty acids and release of lipid peroxides that produce reactive oxygen species (ROS) [12,25].…”

“…Leptin, a peptide hormone produced by adipocytes, acts on the energy balance of reproduction and immunomodulation, and this action is linked to the pathogenesis of many diseases [33,10,26,30,59,60]. Some authors have been discussing about leptin presenting profibrogenic activity in the liver [25,61,62]. High levels of this hormone increase hepatic response to various stimuli of liver fibrosis.…”

“…Leptin has proven to be important in the progression of hepatic steatosis [23,25,26]. As a result of synergistic action of other adipocytokines such as tumor necrosis factor (TNF-α), fatty liver may progress to steatohepatitis by lipoapoptosis induction, which leads to the recruitment of inflammatory cells, contributing to its progression and subsequently causing hepatocellular damage, such as cell swelling and appearance of Mallory bodies [27,25].…”