Sex hormone-binding globulin overexpression protects against high-fat diet-induced obesity in transgenic male mice
Open accessAbstract
Obese subjects of all ages and sex have reduced plasma SHBG levels. Whether these low plasma SHBG levels play a role in obesity development is unknown. In the present work we wanted to explore if SHBG overexpression could prevent obesity development induced by high fat diet (HFD). To do so, we fed humanized SHBG transgenic male mice and their wild-type littermates with control diet (CD) or HFD over the course of 8 weeks. The results showed that SHBG overexpression protected against body weight gain and fat accumulation induced by HFD. In addition, SHBG overexpression also abrogated the increase in insulin, leptin and resistin levels, as well as the reduction in adiponectin, induced by HFD. Mechanistically, the SHBG protection against HFD-induced obesity was achieved by stimulating lipolysis in white adipose tissue. Furthermore, we have demonstrated the SHBG cell-autonomous effect using human primary visceral adipocytes. Taking together, our results demonstrate that SHBG overexpression protects against diet-induced obesity and improves the metabolic profile of male mice fed a HFD diet.
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SHBG overexpression protected male transgenic mice against high-fat-diet-induced obesity and metabolic disease.
“SHBG overexpression protected male, transgenic mice against HFD-induced obesity as well as metabolic disease.”
From Metabolic impact of endogenously produced estrogens by adipose tissue in females and males across the lifespan (2025) · cites this paper as [109]
Section 3.1 reports less HFD-induced weight gain in SHBG transgenic male mice, and Section 3.3 reports improved insulin resistance and several metabolic markers. But the paper does not establish protection against metabolic disease generally: Section 3.3 says SHBG overexpression did not prevent HFD-induced hypercholesterolemia. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSHBG transgenic mice had elevated expression of lipolytic genes including Adrb3, Irf4, and Plin and increased phosphorylation of PKA, ERK-1/2, and HSL.
“SHBG transgenic mice had elevated expression of lipolytic genes including beta-3- adrenergic receptor (Adrb3), interferon regulatory factor-4 (Irf4), and perilipin-1 (Plin) and increased phosphorylation of protein kinase A (PKA), extracellular signal-regulated kinases 1/2 (ERK-1/2), and hormone sensitive lipase (HSL)”
From Metabolic impact of endogenously produced estrogens by adipose tissue in females and males across the lifespan (2025) · cites this paper as [109]
Over 8 weeks, compared to wild-type controls on the same diet, SHBG transgenic mice demonstrated significantly less weight gain, smaller epididymal white adipose tissue depots, and a healthier metabolic profile including lower insulin, leptin, and resistin and higher adiponectin.
“SHBG transgenic mice demonstrated significantly less weight gain, smaller epididymal white adipose tissue (EWAT) depots, and a healthier metabolic profile including lower insulin, leptin, and resistin while also demonstrating higher adiponectin levels (109).”
From Metabolic impact of endogenously produced estrogens by adipose tissue in females and males across the lifespan (2025) · cites this paper as [109]
SHBG may protect against HFD induced obesity through the induction of lipolysis in white adipose tissue, though this finding is contradicted elsewhere.
“may protect against HFD induced obesity through the induction of lipolysis in white adipose tissue, 229 though this finding is contradicted elsewhere.”
From The role of the androgen receptor in the pathogenesis of obesity and its utility as a target for obesity treatments (2022) · cites this paper as [229]
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- Authors
- Saez-Lopez, C., Villena, J. A., Simó, R., & Selva, D. M.
- Affiliations
- Universitat Autònoma de Barcelona (ES)
- Corresponding author
- Selva, David M.
- Venue
- The Journal of Nutritional Biochemistry
- Publisher
- Elsevier BV
- Published
- 2020-11
- Volume
- 85
- Pages
- 108480
- ISSN
- 0955-2863 (ISSN-L)
- OpenAlex
- W3048731959
- Cited by
- 38
- References
- 55
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 7 · 2023: 6 · 2022: 5 · 2021: 4 · 2020: 1
- FWCI
- 2.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The Journal of Nutritional Biochemistry (acceptedVersion)
- PubMed (publishedVersion)
- Funders
- Instituto de Salud Carlos III
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- sex hormone-binding globulin, high-fat diet, diet-induced obesity, white adipose tissue lipolysis, visceral adipocytes, insulin, leptin, resistin, adiponectin, weight gain, adipocyte metabolism, transgenic mice
- MeSH terms
- Animals, Cell Line, Humans, Lipolysis, Male, Mice, Transgenic, Obesity, Sex Hormone-Binding Globulin, Up-Regulation, Diet, High-Fat, Protective Factors
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