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Here we show that adipose Tregs function as a dominant, time-dependent checkpoint on \u03b2-adrenergic signal-driven lipolytic program and signal transduction in adipocytes. Our integrated scRNA-seq, flow cytometry, and phosphoproteomics data show that prolonged adrenergic stimulation induces a progressive attenuation of activation of key lipase hormone-sensitive lipase (HSL) that coincides with Treg depletion in circulation and accumulation within white adipose tissue. Genetic perturbations establish Treg-derived interleukin-10 (IL-10) as the key mediator of this brake. IL-10 signaling through adipocyte IL-10R\u03b1 suppresses adrenergic HSL activation and rewires downstream signaling nodes that govern catecholamine responsiveness, lipolysis, and systemic energy homeostasis. Mechanistically, IL-10R\u03b1 engages a STAT3-dependent transcriptional program that induces the G-protein regulators RGS2 and RGS3, diminished PKA flux to HSL that reinforces suppression of the HSL activation state and lipolysis. Together, these findings define an adrenergic\u2013immune feedback circuit in which Tregs fine tune the amplitude and duration of catecholamine responsiveness in adipocytes, establishing immune control of a core lipolytic pathway with implications for obesity-associated adipose dysfunction.<\/jats:p>","DOI":"10.64898\/2026.07.12.738050","type":"posted-content","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T16:50:20Z","timestamp":1783961420000},"source":"Crossref","is-referenced-by-count":0,"title":["Regulatory T cells establish an IL-10\u2013IL10R\u03b1 immunometabolic checkpoint that limits HSL activation and lipolysis"],"prefix":"10.64898","author":[{"given":"Ramazan","family":"Yildiz","sequence":"first","affiliation":[{"name":"Diabetes, Obesity, and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, New York 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