Abstract
Secreted frizzled-related protein 5 (SFRP5), an antagonist of the noncanonical WNT pathway, has a controversial role in liver disease. The aim of this study was to analyze the role of SFRP5 and the noncanonical WNT pathway in nonalcoholic fatty liver disease (NAFLD). Plasma SFRP5 levels were determined by ELISA in women with normal weight (NW; n = 20) and morbid obesity (MO; n = 69). Women with MO were subclassified according to hepatic histology into normal liver (NL; n = 28), NAFLD (n = 41) (simple steatosis (SS; n = 24), and nonalcoholic steatohepatitis (NASH; n = 17)). We used RT-qPCR to evaluate the hepatic mRNA expression of SFRP5, WNT5A, and JNK in women with MO. SFRP5 levels were lower in NW than in MO patients who underwent a very low-calorie diet before surgery. Hepatic SFRP5 mRNA expression was higher in SS than in NL or NASH; additionally, patients with hepatic inflammation or ballooning presented lower SFRP5 abundance. WNT5A and JNK expression was enhanced in NAFLD compared with NL. In conclusion, circulating SFRP5 levels depend on the diet, and hepatic SFRP5 seems to have a protective role in the first steps of NAFLD; however, SFRP5 could be deregulated in an advanced stage while WNT5A and JNK are activated, promoting liver damage.
Highlights
nonalcoholic fatty liver disease (NAFLD) represents a continuum of liver abnormalities from simple steatosis (SS) to nonalcoholic steatohepatitis (NASH) that can lead to cirrhosis and liver cancer, emerging as an important cause of liver transplant [2,3,4]
(BMI < 25 kg/m2, n = 20) and morbid obesity (MO) (BMI > 40 kg/m2, n = 69). Those with MO were subclassified according to hepatic histology as normal liver (NL; n = 28), SS (n = 24), and NASH (n = 17), which were comparable in terms of weight, body mass index (BMI), insulin, homeostatic model assessment method-insulin resistance (HOMA2-IR), glycosylated hemoglobin (HbA1c), cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), TG, aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), systolic blood pressure (SBP), and diastolic blood pressure (DBP)
When we analyzed the hepatic relative mRNA abundance of WNT5A according to different degrees of NAFLD, we found that WNT5A hepatic expression was significantly enhanced in patients with SS than those with NL or NASH (Figure 5B)
Summary
Nonalcoholic fatty liver disease (NAFLD) is a chronic metabolic disorder of the liver that has emerged as a major public health concern with a high prevalence rate ranging from. NAFLD represents a continuum of liver abnormalities from simple steatosis (SS) to nonalcoholic steatohepatitis (NASH) that can lead to cirrhosis and liver cancer, emerging as an important cause of liver transplant [2,3,4]. The pathogenesis of NAFLD is complicated and involves environmental and genetic factors, hormone secretion, lipid peroxidation damage, immunological reactions, oxidative stress, abnormal fat metabolism, intestinal dysbiosis, and angiogenesis, which induce. NASH and cirrhosis [5]. These mechanisms are not well understood, and effective
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