Finding
Reduced hepatic expression of adipose tissue triglyceride lipase and CGI-58 may contribute to the development of non-alcoholic fatty liver disease in patients with insulin resistance, as their expression was found to be reduced in patients with IR.
Paper
Reduced hepatic expression of adipose tissue triglyceride lipase and CGI-58 may contribute to the development of non-alcoholic fatty liver disease in patients with insulin resistance
Observational Study
Citations: 34
Full text
Semantic ScholarAbstract
TO THE EDITOR: Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of liver dysfunction and is characterized by abnormal accumulation of lipid droplets (LDs) in hepatocytes. This triglyceride (TG) accumulation is caused by increased dietary caloric intake and increased synthesis of fatty acids and TGs, especially in insulin resistance (IR). Despite the efforts of many researchers, no conclusive treatments for NAFLD have yet been established. To develop a novel treatment, a more detailed understanding of the pathogenesis of NAFLD is necessary. Protein components associated with LDs are critical in the regulation of TG hydrolysis and lipid content in LDs. Hormone-sensitive lipase (HSL) and adipose tissue triglyceride lipase (ATGL) differentially regulate this process in adipose tissue [1]. HSL, the rate-limiting lipase for diglyceride (DG) hydrolysis, is activated by PKA-dependent phosphorylation. Conversely, ATGL removes the first fatty acid from TG, generating a free fatty acid and DG. ATGL activity is markedly enhanced by CGI58, a recently identified binding partner for ATGL. The CGI-58 gene is disrupted in Chanarin-Dorfman syndrome, which is characterized by ichthyosis and abnormal fat accumulation in various tissues including liver [2]. The expressions of HSL and ATGL in subcutaneous adipose tissue were reduced in patients with type 2 diabetes, suggesting that these lipases are involved in abnormal fat accumulation in IR [3]. We have previously reported that the expression of HSL is down-regulated in the liver with NAFLD [4]; however, those of ATGL and CGI-58 have not been estimated. To clarify the role of lipolysis in the liver with NAFLD, we estimated the expression of these genes in conjunction with biochemical results. Tissue samples were obtained by liver biopsy from 28 patients with histologically diagnosed NAFLD who were admitted to Kyushu University Hospital between 2004 and 2006. Thirteen insulin-resistant patients were identified (HOMA-IR]2.5). As a control, 10 liver samples were obtained from donor livers, which were normal during biochemical and histological examination; these samples were taken during living donor liver transplantation, which was performed in our hospital. Written consent was obtained from all patients in this investigation. We predicted that patients with NAFLD might show reduced hepatic expression of ATGL and CGI-58; however, there was no significant difference in the expression of these genes between NAFLD and control patients. The influence of IR was also investigated in NAFLD patients. NAFLD patients with IR had higher grades of liver steatosis (45.0916.9% versus 35.5923.3%, p 0.05), significantly higher body mass index (BMI) (29.294.2 versus 24.792.7, p 0.014) and elevated serum alanine aminotransferase (ALAT) (108995.7 IU/l versus 24.9912.8 IU/l, p 0.015) than patients without IR. Interestingly, the expression of ATGL and CGI-58 was reduced in patients with IR (Figure 1). The expression of CGI-58 in patients with IR was significantly reduced to less than 25% of that in patients without IR. The reduced expression of ATGL and CGI-58 was also observed in
Authors
Masaki Kato, N. Higuchi, M. Enjoji
Journal
Scandinavian Journal of Gastroenterology