Sex Hormone-Binding Globulin Expression Correlates with Acetyl-CoA Carboxylase and Triglyceride Content in Human Liver.

Context: There is emerging evidence that sex hormone binding globulin (SHBG) is significantly reduced in chronic metabolic diseases, including obesity and non-alcoholic fatty liver disease (NAFLD). We have recently reported using in vitro (HepG2 cells) and in vivo models (SHBG-C57BL/ksJ-db/db mice) that SHBG could play a role in arresting the progression of NAFLD by downregulating lipogenesis.

Objective: The main aim of this study was to investigate the mechanisms by which SHBG prevents the hepatic lipogenesis by examining the relationship between SHBG and a key lipogenic enzyme such as Acetyl-CoA Carboxylase (ACC) in the liver of obese subjects.

Subjects and Methods: SHBG and ACC mRNA levels, as well as triglyceride (TG) content, were analyzed in 41 liver samples from non-diabetic obese subjects with NAFLD who had undergone bariatric surgery. We also studied the effect of SHBG overexpression in HepG2 cells cultured under high glucose conditions.

Results: SHBG mRNA and protein levels were lower in subjects with metabolic syndrome when compared with subjects without metabolic syndrome; however these differences were only significant at mRNA level. SHBG mRNA levels correlated positively with SHBG protein levels and hepatic triglyceride content. In addition, SHBG mRNA and protein levels correlated negatively with ACC mRNA levels and triglyceride content. Furthermore, SHBG overexpression abrogated the increase in ACC expression induced by high glucose treatment in HepG2 cells.

Conclusions: Our findings suggest that SHBG plays a role in regulating hepatic lipogenesis by reducing ACC levels. These results open up a new strategy for the treatment of NAFLD.