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We investigated a direct lipolytic effect of a specific GLP-1\/GIP\/glucagon receptor triagonist on human adipose tissue to disentangle central and peripheral effects as potential drivers of weight loss.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design and methods<\/jats:title>\n                  <jats:p>Isolated primary adipocytes from subcutaneous adipose tissue biopsies of 22 non-diabetic subjects [63.0 (57.0-69.5) years] were incubated with increasing concentrations of isoprenaline, GLP-1, GIP, glucagon, or a GLP-1\/GIP\/glucagon receptor triagonist. Glycerol concentration was measured following stimulation to assess lipolysis. mRNA expression of adipose tissue receptors was analyzed in parallel.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Glycerol concentration only increased by isoprenaline, GIP (+13%), and GLP-1\/GIP\/glucagon receptor triagonist (+28%) but not by GLP-1 or glucagon. This effect was not related to age or body mass index (BMI). Higher adipose tissue GIP receptor mRNA expression was related to elevated glycerol release after GIP and GLP-1\/GIP\/glucagon receptor triagonist stimulation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Direct lipolytic effects of GIP seem to exist in human subcutaneous adipose tissue. This might be targetable by multiple receptor agonists, especially with a high GIP receptor affinity. Such a mechanism can potentiate the beneficial effect on weight loss and will therefore represent a promising target of future research.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical trial registration number<\/jats:title>\n                  <jats:p>The trial was registered at German Clinical Trials Register (drks.de) as DRKS00010049.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ejendo\/lvae151","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T07:38:32Z","timestamp":1739345912000},"page":"91-99","source":"Crossref","is-referenced-by-count":7,"title":["Hormonal regulation of human adipose tissue lipolysis: impact of adipose GIP system in overweight and obesity"],"prefix":"10.1093","volume":"192","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6336-3939","authenticated-orcid":false,"given":"Sebastian","family":"Brachs","sequence":"first","affiliation":[{"name":"Department of 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