Human sex hormone-binding globulin does not provide metabolic protection against diet-induced obesity and dysglycemia in mice

Yael Sofer, Nava Nevo, Michal Vechoropoulos, Gabi Shefer, Etty Osher, Nathan Landis, Karen Tordjman, Geoffrey L. Hammond, Naftali Stern*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Sex hormone-binding globulin (SHBG) is the main transporter of sex hormones in most vertebrates. Low SHBG levels have been linked to increased risk for diabetes and metabolic syndrome. Polymorphisms of the SHBG gene linked to low SHBG protein levels also strongly predicted increased risk of type 2 diabetes, thus raising the possibility that SHBG may play a role in the pathogenesis of insulin resistance and diabetes. Aim: To examine whether expression of human SHBG in mice may ameliorate the development of diabetes and metabolic syndrome in response to a high-fat diet (HFD). Methods: Transgene mice expressing a human SHBG transgene (SHBG+) (N = 10/11; males/females) and their wild type littermates (N = 12/8; males/females) were fed HFD for 4.5 months. Results: HFD induced comparable obesity in control and SHBG+ mice. Male transgenes had higher muscle mass after 2–3.5 months HFD (0.43 ± 0.028 (n = 4) vs 0.38 ± 0.053 g (n = 7), P = 0.05). Fasting blood glucose, as well as insulin or HOMA-IR, was not different in transgenic vs wild-type males after 4–5 months HFD. Female transgenes had higher fasting glucose (152 ± 29 (n = 7) vs 115 ± 27 mg/dL, P = 0.01 (n = 8)), but mean insulin and HOMA-IR were not different. Likewise, insulin tolerance test and intra-peritoneal glucose tolerance test (GTT) were not different. Finally, SHBG+ mice were not different from controls in terms of liver enzymes, serum triglyceride levels and blood pressure. Conclusion: In mice with diet-induced obesity, human SHBG did not protect against development of obesity or dysglycemia.

Original languageEnglish
Pages (from-to)91-96
Number of pages6
JournalEndocrine Connections
Volume7
Issue number1
DOIs
StatePublished - Jan 2018

Funding

FundersFunder number
Sagol Foundation for the Metabolic Syndrome Research Center

    Keywords

    • Diabetes
    • Metabolic syndrome
    • SHBG

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