{"id":150,"title":"CTRP6-AdipoR1 signaling promotes testosterone production and alleviates obesity-associated male reproductive dysfunction","title_zh":"CTRP6-AdipoR1 信号促进睾酮合成并缓解肥胖相关男性生殖功能障碍","url":"https://pubmed.ncbi.nlm.nih.gov/42987991","doi":"10.1016/j.reprotox.2026.109398","pmid":"42987991","journal":"Reprod Toxicol","kind":"paper","lang":"en","published_at":"2026-11-05T00:00:00+00:00","fetched_at":"2026-11-08T03:43:57+00:00","authors":["Cheng CY","Yu XY","Mu Y"],"primary_topic":"male","topics":[{"slug":"male","score":5.0,"hits":["leydig","male infertility","sperm","spermatogenesis","testicular"]},{"slug":"art-clinical","score":1.0,"hits":["infertility"]},{"slug":"omics-methods","score":1.0,"hits":["transcriptomic"]}],"topic_score":5.0,"preference_score":0.0,"preference_labels":[],"llm_score":78.0,"final_score":78.0,"score_dims":{"novelty":80,"rigor":75,"impact":72,"relevance":88,"translation":65},"recommend_reason":"首次提出间质细胞来源 CTRP6-AdipoR1 自分泌轴连接肥胖与睾酮合成及生精障碍，遗传学与重组蛋白体内挽救实验链条较完整，对男性生育力保护与肥胖相关不育的干预研究有参考价值；但尚属动物模型阶段，向临床转化仍需验证。","keywords":["CTRP6","AdipoR1","睾酮合成","肥胖","男性不育","间质细胞"],"selected":1,"story_id":56,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"pubmed-gametes","source_name":"PubMed · 配子与性腺","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":null,"journal_tier":"unknown","journal_if":null,"is_mock":false,"summary_zh":"该研究探讨肥胖导致男性生育力下降的分子机制。作者发现，C1q/TNF 相关蛋白 6（CTRP6）是由睾丸间质细胞分泌的睾酮合成调控因子，高脂饮食选择性下调间质细胞内 CTRP6 的表达与分泌，而循环水平反而升高，提示睾丸微环境存在组织特异性失调。间质细胞特异性过表达 CTRP6 可缓解高脂饮食诱导的睾丸萎缩、恢复生精小管结构与精子参数并挽救睾酮生成；特异性敲除则损害生精功能。机制上，CTRP6 与 AdipoR1 结合，经 PI3K/Akt、SREBP2-CYP51A1 通路影响胆固醇与睾酮合成；睾丸内注射重组人 CTRP6 可在体内改善生精障碍。","summary":"Obesity is a major risk factor for male infertility, yet the molecular mechanisms linking obesity to impaired spermatogenesis remain poorly defined. Here we show that C1q/TNF-related protein 6 (CTRP6) is a Leydig cell-derived regulator of testosterone production whose local expression is reduced in obesity. High-fat diet (HFD) feeding selectively reduced CTRP6 expression and secretion in Leydig cells despite elevated circulating CTRP6 levels, indicating tissue-specific dysregulation within the testicular microenvironment. Leydig cell-specific CTRP6 overexpression markedly alleviated HFD-induced testicular atrophy, restored seminiferous tubule architecture, improved sperm parameters and reproductive outcomes, and rescued testosterone production. Conversely, Leydig cell-specific CTRP6 knockout impaired spermatogenesis and reduced male reproductive capacity under normal-diet conditions, supporting an important role for endogenous CTRP6 in reproductive homeostasis. The combined secretion, genetic and extracellular-protein experiments are consistent with an autocrine contribution. Transcriptomic analyses identified CYP51A1 as a candidate downstream mediator. CTRP6 associated with adiponectin receptor 1 (AdipoR1), and AdipoR1 knockdown attenuated rhCTRP6-associated changes in PI3K/Akt phosphorylation, SREBP2 and CYP51A1 abundance, cholesterol content and testosterone production. Notably, intratesticular administration of recombinant human CTRP6 (rhCTRP6) effectively rescued HFD-induced spermatogenic dysfunction in vivo. Together, these findings uncover a previously unrecognized local Leydig cell-derived CTRP6 signaling model linking obesity to male reproductive dysfunction.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}