SHBG Overexpression Does Not Prevent High Fat Diet-Induced Obesity, Insulin Resistance and Diabetes

Presentation Number: LBSat-45
Date of Presentation: April 2nd, 2016

Yael Sofer*1, Michal Vechoropoulos2, Etty Osher2, Naftali Stern2 and Geoffrey L Hammond3
1Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, 2Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, 3University of British Columbia, Vancouver, BC, Canada

Abstract

Background: Sex hormone binding globulin (SHBG) is a homodimeric plasma glycoprotein produced by the liver. It acts as the main transporter of biologically active estrogens and androgens in all vertebrae.

Low levels of SHBG have been linked to increased propensity for diabetes and metabolic syndrome. Specific genetic polymorphisms of SHBG gene that were predictive of levels of the SHBG protein, strongly predicted increased risk of type 2 diabetes in both men and women[1][2]. Finally, an association between polymorphism in the SHBG promoter and polycystic ovary syndrome has been suggested[3]. Thus, it seems that the SHBG protein may have an active role in the pathogenesis of diabetes, rather than serving as a mere biomarker[4].

Aims: Analyze whether mice over-expressing human SHBG have lesser tendency to develop diabetes and other characteristics of the metabolic syndrome.

Methods: Transgene mice expressing human SHBG gene and their littermate control wild types mice were fed high fat diet (HFD) for an average of 3 months.

Results: There was no difference in weight of transgene as compared to wild type littermates (Males: 50.01+/-5.71 gr vs 48.745 +/-2.84 gr; females: 39.78+/-8.74 gr vs 45.525+/-7.4 gr, respectively). Male transgenes had significantly higher muscle mass after 2-3.5 month HFD (mean mass 0.43+/-0.028 gr vs 0.38+/-0.053 gr, p=0.05). Fasting blood glucose, as well as insulin or HOMA-IR or HOMA-IR divided by weight were not different in transgenic vs. wild type males (165.5+/-35.63 gr vs 143+/-33.34 gr; 25.67+/-15.57 mIU/L X mg/dl vs 18.93+/-14.61 mIU/L X mg/dl; 0.54 vs 0.41, respectively). Female transgenes had significantly higher fasting glucose (152.28+/-28.73 mg/dl vs 114.5 +/- 27.21 mg/dl, p=0.01), with no difference in average insulin or HOMA-IR and HOMA-IR divided by weight (20.46 +/- 18.73 mIU/L X mg/dl vs 4.04+/-6.3 mIU/L X mg/dl). Insulin tolerance test and glucose tolerance test (GTT) were no different. Overnight GTT was significantly lower in transgenic males (average AUC 24548.75 vs 27218 mg/dl/min). There was no difference in liver enzymes and triglyceride levels and blood pressure values.

Conclusion: In this model of transgenic mice overexpressing human SHBG, this protein showed no protection against diabetes and metabolic syndrome.

 

Nothing to Disclose: YS, MV, EO, NS, GLH