{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wang C"],"funding":["Scientific and Technological Research Project of Xinjiang Production and Construction Corps","Training Program of the Autonomous Region","National Natural Science Foundation of China"],"pagination":["22-36"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12716619"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["75(1)"],"pubmed_abstract":["miRNAs are key regulators of metabolic homeostasis, yet their role in obesity-associated dysfunction remains incompletely understood. Here, we identify miR-432 as a driver of systemic metabolic dysregulation. Serum miRNA profiling revealed a positive correlation between miR-432 expression and obesity/type 2 diabetes mellitus. Functionally, adipose-specific miR-432 exacerbated high-fat diet-induced obesity and insulin resistance. Similarly, hepatic-specific miR-432 aggravated hepatic steatosis and systemic glucose dysregulation, while skeletal muscle-specific miR-432 disrupted glucose homeostasis without affecting body composition. Mechanistically, miR-432 disrupted insulin sensitivity by inhibiting the PIK3R3/AKT pathway and perturbed lipid homeostasis by suppressing the PIK3R3/PPAR-α axis. Notably, obesity-induced miR-432 upregulation was predominantly localized in adipocytes and driven by the CDK5/PPAR-γ axis. Furthermore, adipocyte-derived exosomal miR-432 was identified as a mediator of systemic metabolic dysfunction, facilitating intertissue cross talk in obesity. Collectively, our data demonstrate that miR-432 exacerbates obesity-induced dysregulation of glucose and lipid metabolism.<h4>Article highlights</h4>miR-432 overexpression in adipose tissue, liver, and skeletal muscle exacerbates high-fat diet-induced disruption of metabolic homeostasis. miR-432 impairs glucose homeostasis by suppressing the PIK3R3/AKT pathway and disrupts lipid homeostasis via inhibition of the PIK3R3/PPAR-α axis or directly suppressing PPAR-α. Obesity-induced elevation of miR-432 is predominantly localized in adipocytes and driven by the CDK5/PPAR-γ axis. Adipocyte-derived exosomal miR-432 mediates systemic metabolic dysfunction, establishing an intertissue regulatory network."],"journal":["Diabetes"],"pubmed_title":["miR-432 Exacerbates Obesity-Induced Dysregulation of Glucose and Lipid Homeostasis."],"pmcid":["PMC12716619"],"funding_grant_id":["82260162","81960152","2022AB022","2023ZD037","2023AB057","2021AB028","82160156","2023TSYCCX0116","2022ZD001","2023TSYCQNTJ0032"],"pubmed_authors":["Wang CY","Zhang J","Wang C","Sun C","Xie J","Chu X","Zhang M","Liang M","Hou Y","Wang J"],"additional_accession":[]},"is_claimable":false,"name":"miR-432 Exacerbates Obesity-Induced Dysregulation of Glucose and Lipid Homeostasis.","description":"miRNAs are key regulators of metabolic homeostasis, yet their role in obesity-associated dysfunction remains incompletely understood. Here, we identify miR-432 as a driver of systemic metabolic dysregulation. Serum miRNA profiling revealed a positive correlation between miR-432 expression and obesity/type 2 diabetes mellitus. Functionally, adipose-specific miR-432 exacerbated high-fat diet-induced obesity and insulin resistance. Similarly, hepatic-specific miR-432 aggravated hepatic steatosis and systemic glucose dysregulation, while skeletal muscle-specific miR-432 disrupted glucose homeostasis without affecting body composition. Mechanistically, miR-432 disrupted insulin sensitivity by inhibiting the PIK3R3/AKT pathway and perturbed lipid homeostasis by suppressing the PIK3R3/PPAR-α axis. Notably, obesity-induced miR-432 upregulation was predominantly localized in adipocytes and driven by the CDK5/PPAR-γ axis. Furthermore, adipocyte-derived exosomal miR-432 was identified as a mediator of systemic metabolic dysfunction, facilitating intertissue cross talk in obesity. Collectively, our data demonstrate that miR-432 exacerbates obesity-induced dysregulation of glucose and lipid metabolism.<h4>Article highlights</h4>miR-432 overexpression in adipose tissue, liver, and skeletal muscle exacerbates high-fat diet-induced disruption of metabolic homeostasis. miR-432 impairs glucose homeostasis by suppressing the PIK3R3/AKT pathway and disrupts lipid homeostasis via inhibition of the PIK3R3/PPAR-α axis or directly suppressing PPAR-α. Obesity-induced elevation of miR-432 is predominantly localized in adipocytes and driven by the CDK5/PPAR-γ axis. Adipocyte-derived exosomal miR-432 mediates systemic metabolic dysfunction, establishing an intertissue regulatory network.","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Jan","modification":"2026-06-08T05:29:53.499Z","creation":"2026-06-08T03:08:27.15Z"},"accession":"S-EPMC12716619","cross_references":{"pubmed":["41218910"],"doi":["10.2337/db25-0295"]}}