biostudies-literatureStrieder-Barboza CNIDDK NIH HHSVeterans AffairsNational Institutes of Health665-675https://www.ebi.ac.uk/biostudies/studies/S-EPMC9728465biostudies-literatureUnknown11(1)Obesity-associated type 2 diabetes (DM) leads to adipose tissue dysfunction. Lumican is a proteoglycan implicated in obesity, insulin resistance (IR), and adipocyte dysfunction. Using human visceral adipose tissue (VAT) from subjects with and without DM, we studied lumican effects on adipocyte function. Lumican was increased in VAT and adipocytes in DM. Lumican knockdown in adipocytes decreased lipolysis and improved adipogenesis and insulin sensitivity in VAT adipocytes in DM, while treatment with human recombinant lumican increased lipolysis and impaired insulin-sensitivity in an ERK-dependent manner. We demonstrate that lumican impairs adipocyte metabolism, partially via ERK signalling, and is a potential target for developing adipose tissue-targeted therapeutics in DM.AdipocyteLumican modulates adipocyte function in obesity-associated type 2 diabetes.PMC9728465R01 DK090262R01 DK115190R01DK115190R56 DK132785I01 CX001811Flesher CGEhlers APLumeng CNStrieder-Barboza CGeletka LMEichler TKy AO'Rourke RWAkinleye OfalseLumican modulates adipocyte function in obesity-associated type 2 diabetes.Obesity-associated type 2 diabetes (DM) leads to adipose tissue dysfunction. Lumican is a proteoglycan implicated in obesity, insulin resistance (IR), and adipocyte dysfunction. Using human visceral adipose tissue (VAT) from subjects with and without DM, we studied lumican effects on adipocyte function. Lumican was increased in VAT and adipocytes in DM. Lumican knockdown in adipocytes decreased lipolysis and improved adipogenesis and insulin sensitivity in VAT adipocytes in DM, while treatment with human recombinant lumican increased lipolysis and impaired insulin-sensitivity in an ERK-dependent manner. We demonstrate that lumican impairs adipocyte metabolism, partially via ERK signalling, and is a potential target for developing adipose tissue-targeted therapeutics in DM.2022-01-01T00:00:00Z2022 Dec2025-04-19T06:39:14.877Z2025-04-19T06:39:14.877ZS-EPMC97284653645725610.1080/21623945.2022.2154112