Sex Hormone–Binding Globulin Expression Correlates With Acetyl-Coenzyme A Carboxylase and Triglyceride Content in Human Liver

Abstract Context There is emerging evidence that SHBG is substantially reduced in chronic metabolic diseases, including obesity and nonalcoholic fatty liver disease (NAFLD). We have recently reported, through use of in vitro (HepG2 cells) and in vivo (SHBG-C57BL/ksJ-db/db mice) models, that SHBG cou...

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Published in:The journal of clinical endocrinology and metabolism 2019-05, Vol.104 (5), p.1500-1507
Main Authors: Sáez-López, Cristina, Salcedo-Allende, Maria Teresa, Hernandez, Cristina, Simó-Servat, Olga, Simó, Rafael, Selva, David M
Format: Article
Language:English
Subjects:
Acetyl-CoA Carboxylase - genetics
Acetyl-CoA Carboxylase - metabolism
Adult
Animal models
Biomarkers - analysis
Case-Control Studies
Coenzyme A
Dextrose
Enzymes
Fatty liver
Fatty Liver - physiopathology
Female
Follow-Up Studies
Gastrointestinal surgery
Globulins
Glucose
Hep G2 Cells
Hormones
Humans
Lipogenesis
Liver
Liver diseases
Male
Metabolic syndrome
Metabolic Syndrome - diagnosis
Metabolic Syndrome - etiology
Metabolic Syndrome - metabolism
Middle Aged
mRNA
Non-alcoholic Fatty Liver Disease - physiopathology
Obesity
Obesity - complications
Patients
Prognosis
Proteins
RNA
Sex Hormone-Binding Globulin - genetics
Sex Hormone-Binding Globulin - metabolism
Sex hormones
Surgery
Thiols
Triglycerides
Triglycerides - blood
Type 2 diabetes
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Summary:Abstract Context There is emerging evidence that SHBG is substantially reduced in chronic metabolic diseases, including obesity and nonalcoholic fatty liver disease (NAFLD). We have recently reported, through use of in vitro (HepG2 cells) and in vivo (SHBG-C57BL/ksJ-db/db mice) models, 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 hepatic lipogenesis by examining the relationship between SHBG and a key lipogenic enzyme, such as acetyl-coenzyme A carboxylase (ACC) in the liver of obese persons. Participants and Methods SHBG and ACC mRNA levels, as well as triglyceride content, were analyzed in 41 liver samples from nondiabetic obese patients 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 patients with metabolic syndrome than in those without metabolic syndrome; however, these differences were significant only for 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 suggest a strategy for the treatment of NAFLD. SHBG regulates ACC, a key enzyme of hepatic lipogenesis. The SHBG reduction that occurs in obesity may play a role in NAFLD. Thus, SHBG could be a therapeutic target against NAFLD.
ISSN:0021-972X
1945-7197
DOI:10.1210/jc.2018-00740