Hematopoietic androgen receptor deficiency promotes visceral fat deposition in male mice without impairing glucose homeostasis
Open accessAbstract
Androgen deficiency in men increases body fat, but the mechanisms by which testosterone suppresses fat deposition have not been elucidated fully. Adipose tissue macrophages express the androgen receptor (AR) and regulate adipose tissue remodeling. Thus, testosterone signaling in macrophages could alter the paracrine function of these cells and thereby contribute to the metabolic effects of androgens in men. A metabolic phenotyping study was performed to determine whether the loss of AR signaling in hematopoietic cells results in greater fat accumulation in male mice. C57BL/6J male mice (ages 12-14 weeks) underwent bone marrow transplant from either wild-type (WT) or AR knockout (ARKO) donors (n = 11-13 per group). Mice were fed a high-fat diet (60% fat) for 16 weeks. At baseline, 8 and 16 weeks, glucose and insulin tolerance tests were performed, and body composition was analyzed with fat-water imaging by MRI. No differences in body weight were observed between mice transplanted with WT bone marrow [WT(WTbm)] or ARKO bone marrow [WT(ARKObm)] prior to initiation of the high-fat diet. After 8 weeks of high-fat feeding, WT(ARKObm) mice exhibited significantly more visceral and total fat mass than WT(WTbm) animals. Despite this, no differences between groups were observed in glucose tolerance, insulin sensitivity, or plasma concentrations of insulin, glucose, leptin, or cholesterol, although WT(ARKObm) mice had higher plasma levels of adiponectin. Resultant data indicate that AR signaling in hematopoietic cells influences body fat distribution in male mice, and the absence of hematopoietic AR plays a permissive role in visceral fat accumulation. These findings demonstrate a metabolic role for AR signaling in marrow-derived cells and suggest a novel mechanism by which androgen deficiency in men might promote increased adiposity. The relative contributions of AR signaling in macrophages and other marrow-derived cells require further investigation.
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WT mice receiving ARKO bone marrow exhibited significantly higher visceral and total fat mass than WT mice receiving WT bone marrow when fed a HFD.
“WT mice receiving ARKO bone marrow exhibited significantly higher visceral and total fat mass than WT mice receiving WT bone marrow when fed a HFD diet.”
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 [157]
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- Authors
- Rubinow, K. B., Wang, S., den Hartigh, L. J., Subramanian, S., Morton, G. J., Buaas, F. W., Lamont, D., Gray, N., Braun, R. E., & Page, S. T.
- Affiliations
- University of Washington (US)
- Division of Metabolism, Endocrinology, and Nutrition; Department of Medicine; University of Washington School of Medicine; Seattle WA USA
- Jackson Laboratory (US)
- Corresponding author
- Rubinow, K. B.
- Venue
- Andrology
- Publisher
- Wiley
- Published
- 2015-06-20
- Volume
- 3
- Issue
- 4
- Pages
- 787-796
- ISSN
- 2047-2919 (ISSN-L)
- PMC
- PMC4736737
- OpenAlex
- W1863098067
- Cited by
- 16
- References
- 49
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2018: 3 · 2017: 2 · 2016: 2
- FWCI
- 1.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Andrology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Funders
- National Institutes of Health (6K12 HD053984, K01 ATT007177, DK089056, HD042454)
- American Heart Association (Clinical Research Program)
- University of Washington (P30 DK035816, Robert B. McMillen Professorship)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- androgen receptor, hematopoietic cells, visceral fat deposition, androgen deficiency, testosterone, adipose tissue macrophages, bone marrow transplantation, adiponectin, glucose homeostasis, insulin sensitivity, high-fat diet, adiposity, body fat distribution
- MeSH terms
- Animals, Bone Marrow Cells, Glucose, Insulin Resistance, Liver, Macrophages, Male, Mice, Inbred C57BL, Random Allocation, Receptors, Androgen, Adipocytes, Mice, Knockout, Paracrine Communication, Intra-Abdominal Fat, Adiposity, Lipogenesis, Adiponectin, Diet, High-Fat
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