ArticleEndocrinology2021
Testosterone Reduces Body Fat in Male Mice by Stimulation of Physical Activity Via Extrahypothalamic ERα Signaling.
Article in Endocrinology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 18 citations in OpenAlex.
- Sex-Specific Metabolic Footprint of Ketogenic Diet in C57BL/6J Mice.Biomedicines · 2026Article
- Hormones, heat, and health: a comprehensive review of sex-based differences in brown and beige fat biology.Biology of sex differences · 2025Review
- Testosterone and Obesity in an Aging Society.Biomolecules · 2025Review
- The role of androgens and global and tissue-specific androgen receptor expression on body composition, exercise adaptation, and performance.Biology of sex differences · 2025Review
- Guidelines on the use of sex and gender in cardiovascular research.American journal of physiology. Heart and circulatory physiology · 2024Review
- Castration promotes the browning of the prostate tumor microenvironment.Cell communication and signaling : CCS · 2023Article
- Thermogenic Brown Fat in Humans: Implications in Energy Homeostasis, Obesity and Metabolic Disorders.The world journal of men's health · 2023Review
- The IP6K Inhibitor LI-2242 Ameliorates Diet-Induced Obesity, Hyperglycemia, and Hepatic Steatosis in Mice by Improving Cell Metabolism and Insulin Signaling.Biomolecules · 2023Article
- Sexual Dimorphism in Adipose-Hypothalamic Crosstalk and the Contribution of Aryl Hydrocarbon Receptor to Regulate Energy Homeostasis.International journal of molecular sciences · 2022Review
- The role of the androgen receptor in the pathogenesis of obesity and its utility as a target for obesity treatments.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2022Review
- Insights of the role of estrogen in obesity from two models of ERα deletion.Journal of molecular endocrinology · 2022Article
- Skeletal muscle wasting: the estrogen side of sexual dimorphism.American journal of physiology. Cell physiology · 2022Review
- The androgen receptor depends on ligand-binding domain dimerization for transcriptional activation.EMBO reports · 2021Article
- Extrahypothalamic ER Alpha Are Required for Testosterone Effects on Physical Activity and Fat Mass in Mice.Endocrinology · 2021Article
- Sex Differences in Brown Adipose Tissue Function: Sex Hormones, Glucocorticoids, and Their Crosstalk.Frontiers in endocrinology · 2021Review
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Authors and funding
15 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Testosterone (T) reduces male fat mass, but the underlying mechanisms remain elusive, limiting its clinical relevance in hypogonadism-associated obesity. Here, we subjected chemically castrated high-fat diet-induced adult obese male mice to supplementation with T or the nonaromatizable androgen dihydrotestosterone (DHT) for 20 weeks. Both hormones increased lean mass, thereby indirectly increasing oxygen consumption and energy expenditure. In addition, T but not DHT decreased fat mass and increased ambulatory activity, indicating a role for aromatization into estrogens. Investigation of the pattern of aromatase expression in various murine tissues revealed the absence of Cyp19a1 expression in adipose tissue while high levels were observed in brain and gonads. In obese hypogonadal male mice with extrahypothalamic neuronal estrogen receptor alpha deletion (N-ERαKO), T still increased lean mass but was unable to decrease fat mass. The stimulatory effect of T on ambulatory activity was also abolished in N-ERαKO males. In conclusion, our work demonstrates that the fat-burning action of T is dependent on aromatization into estrogens and is at least partially mediated by the stimulation of physical activity via extrahypothalamic ERα signaling. In contrast, the increase in lean mass upon T supplementation is mediated through the androgen receptor and indirectly leads to an increase in energy expenditure, which might also contribute to the fat-burning effects of T.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.