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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 contrast, castrated male mice expressed significantly decreased ApN levels, while, in cell cultures, adding testosterone reduced both circulating ApN and ApN secretion.[63,65] This treatment also induces insulin resistance.”
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“Testosterone therapy has also been shown to reduce adiponectin concentrations in both sham-operated and castrated mice as well as in cultured adipocytes ( 26 ).”
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“Numerous studies have shown that APN plays an important role in glucose and lipid metabolism [28], insulin sensitization [29], vascular protection [30] and exerting anti-atherosclerosis ef-”
BackgroundInfluence of gender, age and renal function on plasma adiponectin level: the Tanno and Sobetsu study
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“On the other hand, it may be because androgen inhibits the production of adiponectin that adiponectin is lower in males than in females ( 37 ).”
BackgroundMethodTsai, P., Yu, C., Hsu, S., Lee, Y., Chiou, C., Hsu, Y., Ho, S., & Chu, C. (2004) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2004.02057.x · Cited by 187
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Self-citationUnderstanding androgen action in adipose tissue
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“The same authors also described in humans lower plasma adiponectin levels in male in comparison to female subjects (Nishizawa et al., 2002).”
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The regulation of adipose tissue health by estrogens
Steiner, B. M., & Berry, D. C. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.889923 · Cited by 171
Adiponectin before and after Weight Loss in Obese Children
Reinehr, T., Roth, C. L., Menke, T., & Andler, W. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031925 · Cited by 172
Smitka, K., & Maresova, D. (2015) · Prague Medical Report · doi:10.14712/23362936.2015.49 · Cited by 178
“However, Nishizawa et al. (2002) documented that testosterone leads to a reduction in plasma adiponectin in men.”
BackgroundRegional differences of insulin action in adipose tissue: insights from in vivo and in vitro studies
Giorgino, F., Laviola, L., & Eriksson, J. W. (2005) · Acta Physiologica Scandinavica · doi:10.1111/j.1365-201x.2004.01385.x · Cited by 230
Liu, Y., Schultz, J. J., & Brent, G. A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306120200 · Cited by 165
The relationship between gut and adipose hormones, and reproduction
Comninos, A. N., Jayasena, C. N., & Dhillo, W. S. (2013) · Human Reproduction Update · doi:10.1093/humupd/dmt033 · Cited by 169
“This latter effect is supported by the findings of higher plasma adiponectin levels in castrated mice while testosterone replacement reduces adiponectin levels in both sham-operated and these castrated mice (Nishizawa et al., 2002).”
InfluentialCardiovascular disease in the polycystic ovary syndrome: New insights and perspectives
Cussons, A. J., Stuckey, B. G. A., & Watts, G. F. (2005) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2005.10.007 · Cited by 165
Plasma adiponectin and insulin resistance in women with polycystic ovary syndrome
Ardawi, M. S. M., & Rouzi, A. A. (2005) · Fertility and Sterility · doi:10.1016/j.fertnstert.2004.11.077 · Cited by 165
Weigert, J., Obermeier, F., Neumeier, M., Wanninger, J., Filarsky, M., Bauer, S., Aslanidis, C., Rogler, G., Ott, C., Schäffler, A., et al. (2009) · Inflammatory Bowel Diseases · doi:10.1002/ibd.21091 · Cited by 163
“Testosterone decreased plasma adiponectin in mice and metronidazole may lower testosterone levels in males and thereby may also contribute to elevated adiponectin concentrations in males.(46,49) Chemerin, however, was significantly elevated only in the serum of female UC patients treated with corticosteroids.”
BackgroundTestosterone Administration Suppresses Adiponectin Levels in Men
Page, S. T., Herbst, K. L., Amory, J. K., Coviello, A. D., Anawalt, B. D., Matsumoto, A. M., & Bremner, W. J. (2005) · Journal of Andrology · doi:10.1002/j.1939-4640.2005.tb02876.x · Cited by 162
Associations of adipokines with asthma, rhinoconjunctivitis, and eczema in German schoolchildren
Nagel, G., Köenig, W., Rapp, K., Wabitsch, M., Zoellner, I., & Weiland, S. K. (2008) · Pediatric Allergy and Immunology · doi:10.1111/j.1399-3038.2008.00740.x · Cited by 162
“4 lg/ml), but clearly lower adiponectin levels are seen in men than in women (13), which can be explained by hormonal status in adults (33).”
BackgroundSex differences in energy metabolism: natural selection, mechanisms and consequences
Mauvais‐Jarvis, F. (2023) · Nature Reviews Nephrology · doi:10.1038/s41581-023-00781-2 · Cited by 174
Sexual Dimorphism and Regulation of Resistin, Adiponectin, and Leptin Expression in the Mouse
Gui, Y., Silha, J. V., & Murphy, L. J. (2004) · Obesity Research · doi:10.1038/oby.2004.185 · Cited by 155
Serum Levels of the Adipokine Vaspin in Relation to Metabolic and Renal Parameters
Seeger, J., Ziegelmeier, M., Bachmann, A., Lössner, U., Kratzsch, J., Blüher, M., Stümvoll, M., & Faßhauer, M. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-1853 · Cited by 153
Novel Expression and Direct Effects of Adiponectin in the Rat Testis
Caminos, J. E., Nogueiras, R., Gaytán, F., Pineda, R., González, C. R., Barreiro, M. L., Castano, J. P., Malagón, M. M., Pinilla, L., Toppari, J., et al. (2008) · Endocrinology · doi:10.1210/en.2007-1582 · Cited by 153
“than in males (38) and that androgens inhibit adiponectin secretion (39, 40).”
BackgroundRundek, T., Gardener, H. E., Xu, Q., Goldberg, R. B., Wright, C. B., Boden-Albala, B. M., Disla, N., Paik, M. C., Elkind, M. S. V., & Sacco, R. L. (2010) · Archives of Neurology · doi:10.1001/archneurol.2010.235 · Cited by 148
Adiponectin as a routine clinical biomarker
Kishida, K., Funahashi, T., & Shimomura, I. (2013) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2013.08.006 · Cited by 149
Self-citationEffects of Growth Hormone (GH) on Ghrelin, Leptin, and Adiponectin in GH-Deficient Patients
Engström, B. E., Burman, P., Holdstock, C., & Karlsson, F. A. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030713 · Cited by 146
Bullen, J. W., Blüher, S., Kelesidis, T., & Mantzoros, C. S. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00245.2006 · Cited by 145
“There are sex differences in plasma levels of adiponectin in rodents and in humans, with higher values in females than in males (9, 18, 27).”
BackgroundAdiponectin Levels and Genotype: A Potential Regulator of Life Span in Humans
Atzmon, G., Pollin, T. I., Crandall, J. P., Tanner, K., Schechter, C. B., Scherer, P. E., Rincón, M., Siegel, G., Katz, M., Lipton, R. B., et al. (2008) · The Journals of Gerontology Series A · doi:10.1093/gerona/63.5.447 · Cited by 146
Metabolic Actions of Adipocyte Hormones: Focus on Adiponectin
Ahima, R. S. (2006) · Obesity · doi:10.1038/oby.2006.276 · Cited by 147
“Moreover, women have higher proportions of high molecular weight adiponectin than men (24).”
BackgroundInflammation, adiponectin, obesity and cardiovascular risk
Mangge, H., Almer, G., Truschnig-Wilders, M., Schmidt, A., Gasser, R., & Fuchs, D. (2010) · Current Medicinal Chemistry · doi:10.2174/092986710794183006 · Cited by 142
Ageing and plasma adiponectin concentration in apparently healthy males and females
Adamczak, M., Rzepka, E., Chudek, J. T., & Więcek, A. (2004) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2004.02182.x · Cited by 141
Kotani, Y., Yokota, I., Kitamura, S., Matsuda, J., Naito, E., & Kuroda, Y. (2004) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2004.02041.x · Cited by 153
“It is possible that this difference originates in the difference in the testosterone level, which decreases the plasma adiponectin concentration through its effect on the secretion of adiponectin from adipocytes (Nishizawa et al., 2002).”
BackgroundAssociation of Hypoadiponectinemia With Smoking Habit in Men
Iwashima, Y., Katsuya, T., Ishikawa, K., Kida, I., Ohishi, M., Horio, T., Ouchi, N., Ohashi, K., Kihara, S., Funahashi, T., et al. (2005) · Hypertension · doi:10.1161/01.hyp.0000169444.05588.4c · Cited by 138
Self-citationDiamanti‐Kandarakis, E. (2006) · Endocrine · doi:10.1385/endo:30:1:13 · Cited by 136
Kanazawa, I., Yamaguchi, T., Tada, Y., Yamauchi, M., Yano, S., & Sugimoto, T. (2010) · Bone · doi:10.1016/j.bone.2010.12.020 · Cited by 137
“It has been shown that androgen decreased plasma adiponectin level via its effect on adipocyte in male mice [27].”
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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