2025/02/01 by Sebastian Brachs, Dominik Soll, Finja Beer +5 · 1 voice
Medicine · #Adipokines, Inflammation, and Metabolic Diseases #Diabetes Treatment and Management #Adipose Tissue and Metabolism
paper · doi:10.1093/ejendo/lvae151
openalex publication_date 2025/02/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31
OBJECTIVE: Given the promising effects of GLP-1/GIP/glucagon receptor triagonists on weight loss in animals and humans, improved understanding of underlying mechanism is required. 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. DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. CLINICAL TRIAL REGISTRATION NUMBER: The trial was registered at German Clinical Trials Register (drks.de) as DRKS00010049.