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Although such a phenomenon can be readily explained by estrogen\u2019s direct action on adipocytes in women, accumulative evidence does not support the direct action of testosterone in adipocyte lipid metabolism, suggesting there is a missing intermediary link. Herein, we propose that glycoprotein hormone \u03b25 (GPHB5) is the intermediary linkage between testosterone and the regulation of adiposity. In clinical samples, blood levels of GPHB5 were correlated negatively with men\u2019s ages and positively with circulating testosterone. Testosterone directly stimulated the expression of GPHB5 in cultured cells; pharmacological blockade of androgen receptor (AR) functions abrogated this effect. Knockout of AR led not only to development of obesity but also reduction of GPHB5 expression. Genetic ablation of GPHB5 in men, but not women, reduced the browning of white adipose tissue, diminished energy expenditure, and caused severe obesity. Importantly, elevated blood testosterone levels did not exert catabolic actions in GPHB5\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mice; yet, recombinant GPHB5 protein could stimulate energy expenditure and reduce adiposity. These results provide strong proof that GPHB5 is the \u201cmissing\u201d intermediary hormone linking testosterone (and aging) and its well-known catabolic effect on adipose tissue.\n                  <\/jats:p>","DOI":"10.1172\/jci192355","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T17:00:41Z","timestamp":1770138041000},"source":"Crossref","is-referenced-by-count":1,"title":["Reduced glycoprotein hormone \u03b25 links male aging and testosterone decline to increased adiposity"],"prefix":"10.1172","volume":"136","author":[{"given":"Gengmiao","family":"Xiao","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China."},{"name":"Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, 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