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Androgens Decrease Plasma Adiponectin, an Insulin-Sensitizing Adipocyte-Derived Protein
Abstract
Adiponectin, an adipose-specific secretory protein, exhibits antidiabetic and antiatherogenic properties. In the present study, we examined the effects of sex hormones on the regulation of adiponectin production. Plasma adiponectin concentrations were significantly lower in 442 men (age, 52.6 ± 11.9 years [mean ± SD]) than in 137 women (53.2 ± 12.0 years) but not different between pre- and postmenopausal women. In mice, ovariectomy did not alter plasma adiponectin levels. In contrast, high levels of plasma adiponectin were found in castrated mice. Testosterone treatment reduced plasma adiponectin concentration in both sham-operated and castrated mice. In 3T3-L1 adipocytes, testosterone reduced adiponectin secretion into the culture media, using pulse-chase study. Castration-induced increase in plasma adiponectin was associated with a significant improvement of insulin sensitivity. Our results indicate that androgens decrease plasma adiponectin and that androgen-induced hypoadiponectinemia may be related to the high risks of insulin resistance and atherosclerosis in men.
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“The two major adipokines, leptin and adiponectin, are characterized by higher circulating levels in women than men [14, 15].”
From Sex differences in metabolic homeostasis, diabetes, and obesity (2015) · cites this paper as [15]
In the citing paper
“Testosterone has been reported to regulate the secretion of metabolic factors such as adiponectin 240 and leptin. 241”
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 [240]
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“In general, the adiponectin level was higher in females than in males, which supports earlier reports [27–29].”
ResultStructure, Signalling and Physiologic Role of Adiponectin-Dietary and Exercise- Related Variations
Hickman, I. J., & Whitehead, J. P. (2012) · Current Medicinal Chemistry · doi:10.2174/092986712803833155 · Cited by 19
Leptin Is Associated with Mood Status and Metabolic Homeostasis in Patients with Bipolar Disorder
Lee, H. J., Kim, S. H., Kim, E. Y., Lee, N. Y., Yu, H. Y., Kim, Y. S., & Ahn, Y. M. (2014) · Neuropsychobiology · doi:10.1159/000366488 · Cited by 18
Adiponectin/resistin levels and insulin resistance in children: a four country comparison study
Takemoto, K., Deckelbaum, R. J., Saito, I., Likitmaskul, S., Morandi, A., Pinelli, L., Ishii, E., Kida, K., & Abdalla, M. (2015) · International Journal of Pediatric Endocrinology · doi:10.1186/1687-9856-2015-2 · Cited by 20
Kwak, M., Kim, E., Jang, E. J., & Lee, C. (2017) · Respirology · doi:10.1111/resp.13127 · Cited by 18
Potential Roles of Adiponectin Isoforms in Human Obesity with Delayed Wound Healing
Ryu, J., Loza, C., Xu, H. Y., Zhou, M., Hadley, J. T., Wu, J., You, H., Wang, H., Yang, J., Bai, J., et al. (2019) · Cells · doi:10.3390/cells8101134 · Cited by 20
“9–17 μg/mL) [22], women have significantly higher levels of adiponectin compared with men [47].”
BackgroundKim‐Mitsuyama, S., Soejima, H., Yasuda, O., Node, K., Jinnouchi, H., Yamamoto, E., Sekigami, T., Ogawa, H., & Matsui, K. (2019) · Scientific Reports · doi:10.1038/s41598-019-52977-x · Cited by 22
Soares, M. J., Cummings, N. K., & Ping‐Delfos, W. C. S. (2011) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2012.03.003 · Cited by 18
Takemoto, F., Katori, H., Sawa, N., Hoshino, J., Suwabe, T., Nakanishi, S., Arai, S., Fukuda, S., Kodaka, K., Shimada, M., et al. (2008) · Nephron Clinical Practice · doi:10.1159/000178818 · Cited by 18
“recently reported that plasma adiponectin was correlated significantly and negatively with visceral fat area in HD patients. Moreover, the gender difference may be partly attributed by sex hormones such as testosterone, which has been reported to reduce plasma adiponectin concentrations [”
BackgroundSelf-citationMatsuda, Y., Tanioka, T., Yoshioka, T., Nagano, T., Hiroi, T., YOSHIKAWA, K., Okabe, K.-I., Nagamine, I., & Takasaka, Y. (2005) · Psychiatry and Clinical Neurosciences · doi:10.1111/j.1440-1819.2005.01370.x · Cited by 18
“reports that an effect of testosterone which makes plasma adiponectin lower is responsible for the gender difference in adiponectin levels.(31) Baptista et al.”
BackgroundAdipose-androgen crosstalk in polycystic ovary syndrome: mechanisms and therapeutic implications
Ni, M., Lei, H., Ye, T., & Wang, Y. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1731179 · Cited by 25
Hirata, A., Kishida, K., Nakatsuji, H., Kobayashi, H., Funahashi, T., & Shimomura, I. (2012) · Metabolism · doi:10.1016/j.metabol.2012.10.011 · Cited by 17
“[24] Nishizawa H, Shimomura I, Kishida K, et al.”
BackgroundSelf-citationThe Role of Adiponectin in the Pathogenesis of Metabolic Disturbances in Patients With Schizophrenia
Chen, C. Y.-A., Goh, K. K., Chen, C.-H., & Lu, M. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.605124 · Cited by 18
“In both animal and human studies, females show higher total and HMWadiponectin levels than males (27, 125–127), which may be contributed to the effect of androgens (126).”
BackgroundEffect of estrogen therapy on adipocytokines in ovariectomized‐aged rats
Kafkas, S., Dost, T., Ozkayran, H., Yenisey, Ç., Tunçyürek, P., & Birincioğlu, M. (2011) · Journal of obstetrics and gynaecology research · doi:10.1111/j.1447-0756.2011.01696.x · Cited by 17
“Testosterone reduces the production of adiponectin in plasma, which may be related to the high risks of insulin resistance and atherosclerosis in men.(23) Circulating adiponectin concentrations in women with postmenopausal mammary cancer are lower compared with controls.”
BackgroundCicero, A. F. G., Magni, P., Morè, M., Ruscica, M., Borghi, C., & Strollo, F. (2012) · Obesity Facts · doi:10.1159/000339575 · Cited by 17
Marousi, S., Theodorou, G., Καρακάντζα, Μ., Papathanasopoulos, P., & Ellul, J. (2009) · Acta Neurologica Scandinavica · doi:10.1111/j.1600-0404.2009.01231.x · Cited by 17
“circulating ADPN in females has been also previously observed (5), and has been attributed to an estrogen action (29).”
BackgroundKotnik, P., Fischer‐Posovszky, P., & Wabitsch, M. (2015) · Slovenian Journal of Public Health · doi:10.1515/sjph-2015-0020 · Cited by 17
“In contrast to RBP4, their levels are lower in males compared to females, and further studies demonstrated that the male sex hormone testosterone inhibited the expression of leptin and adiponectin in adipocytes (11, 103).”
ResultLeptin, Ghrelin, and Adiponectin Evaluation in Transsexual Subjects During Hormonal Treatments
Resmini, E., Andraghetti, G., Rebora, A., Cordera, R., Vera, L., Giusti, M., Minuto, F. M., & Ferone, D. (2008) · Journal of Andrology · doi:10.2164/jandrol.108.004952 · Cited by 17
Experimental Melanin-Induced Uveitis: Experimental Model of Human Acute Anterior Uveitis
Smith, J. R., Rosenbaum, J. T., & Williams, K. A. (2008) · Ophthalmic Research · doi:10.1159/000119864 · Cited by 17
Franco, C., Koranyi, J., Brandberg, J., Lönn, L., Bengtsson, B., Svensson, J., & Johannsson, G. (2008) · Growth Hormone & IGF Research · doi:10.1016/j.ghir.2008.07.001 · Cited by 17
Chen, T., Tu, M., Huang, L., & Zheng, Y. (2020) · Journal of Diabetes Research · doi:10.1155/2020/4739271 · Cited by 17
“proposed that high levels of androgenic hormone in males might lead to the result [39], but a recent study found that sex differences still existed even when men were compared with postmenopausal women [40].”
ResultRubinow, 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. (2015) · Andrology · doi:10.1111/andr.12055 · Cited by 16
“Higher plasma levels of adiponectin also have been found in men after testosterone deprivation (Rubinow et al., 2012) whereas androgen administration suppresses adiponectin secretion (Nishizawa et al., 2002; Page et al., 2005).”
Chattopadhyay, S., Joharapurkar, A. A., Das, N., Khatoon, S., Kushwaha, S., Gurjar, A. A., Singh, A. K., Shree, S., Ahmed, M. Z., China, S. P., et al. (2021) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2021.111525 · Cited by 16
Impact of puberty, sex determinants and chronic inflammation on cardiovascular risk in young people
Allalou, A., Peng, J., Robinson, G., Marruganti, C., D’Aiuto, F., Butler, G. E., Jury, E. C., & Ciurtin, C. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2023.1191119 · Cited by 19
Urushima, H., Inomata-Kurashiki, Y., Nishimura, K., Sumi, R., Shimomura, I., Nonomura, N., Ito, T., & Maeda, K. (2015) · The Aging Male · doi:10.3109/13685538.2015.1017809 · Cited by 16
“Although androgens decrease serum adiponectin levels, androgen-induced hypoadiponectinemia may be related to an increased risk of insulin resistance and atherosclerosis in men [14].”
BackgroundSelf-citationTotal and high molecular weight adiponectin in patients with coronary artery disease
El-Menyar, A. A., Rizk, N. M., Nabti, A., Hassira, S. A., Singh, R., Rahman, M. O. A., & Suwaidi, J. M. S. A. (2009) · Journal of Cardiovascular Medicine · doi:10.2459/jcm.0b013e3283252b50 · Cited by 16
Blunted Blood Pressure Response and Elevated Plasma Adiponectin Levels in Female Sprague Dawley Rats
Kamari, Y., Peleg, E., Leibowitz, A., & Grossman, E. (2012) · American Journal of Hypertension · doi:10.1038/ajh.2011.260 · Cited by 16
“32 Xu et al. 33 showed that high molecular weight adiponectin was significantly higher in female mice than in males and testosterone treatment caused a specific reduction of high molecular weight adiponectin in the circulation.”
BackgroundCicero, A. F. G., Magni, P., Morè, M., Ruscica, M., Dozio, E., Steffani, L., Borghi, C., & Strollo, F. (2011) · International Journal of Endocrinology · doi:10.1155/2011/724816 · Cited by 16
“While in rodents, testosterone injection decreases adiponectin levels, [12] in healthy adult-elderly humans, [13] and in women affected by polycystic ovary syndrome, [14] serum adiponectin and testosterone are directly correlated.”
BackgroundThe evolving role of adiponectin as an additive biomarker in HFrEF
Sente, T., Gevaert, A. B., Berendoncks, A. V., Vrints, C. J., & Hoymans, V. Y. (2016) · Heart Failure Reviews · doi:10.1007/s10741-016-9578-z · Cited by 16
“This sexual dimorphism has been attributed to the inhibiting effect of testosterone on the secretion of adiponectin and the higher body fat percentage observed in women [27, 28].”
Background
Metadata
- Authors
- Nishizawa, H., Shimomura, I., Kishida, K., Maeda, N., Kuriyama, H., Nagaretani, H., Matsuda, M., Kondo, H., Furuyama, N., Kihara, S., Nakamura, T., Tochino, Y., Funahashi, T., & Matsuzawa, Y.
- Affiliations
- The University of Osaka (JP)
- From the Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Suita, Japan
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2002-09-01
- Volume
- 51
- Issue
- 9
- Pages
- 2734-2741
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2102610155
- Cited by
- 837
- References
- 44
- Citations by year
- 2026: 13 · 2025: 18 · 2024: 7 · 2023: 32 · 2022: 19 · 2021: 28 · 2020: 25 · 2019: 32 · 2018: 34 · 2017: 24 · 2016: 21 · 2015: 41 · 2014: 46 · 2013: 43 · 2012: 51
- FWCI
- 28.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- adiponectin, androgens, testosterone, sex hormones, insulin sensitivity, insulin resistance, atherosclerosis, hypoadiponectinemia, ovariectomy, castration, adipocytes, 3T3-L1 adipocytes, sex differences, menopause
- MeSH terms
- Adult, Androgens, Animals, Female, Humans, Insulin, Male, Mice, Inbred C57BL, Mice, Inbred ICR, Middle Aged, Ovariectomy, Proteins, Sex Characteristics, Testosterone, 3T3 Cells, Adipocytes, Postmenopause, Intercellular Signaling Peptides and Proteins, Mice, Adiponectin
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