Print Email Facebook Twitter Salsalate activates brown adipose tissue in mice Title Salsalate activates brown adipose tissue in mice Author van Dam, A.D. Nahon, K.J. Kooijman, S. van den Berg, S.M. Kanhai, A.A. Kikuchi, T. Heemskerk, M.M. van Harmelen, V. Lombès, M. van den Hoek, A.M. de Winther, M.P. Lutgens, E. Guigas, B. Rensen, P.C. Boon, M.R. Publication year 2015 Abstract Salsalate improves glucose intolerance and dyslipidemia in type 2 diabetes patients, but the mechanism is still unknown. The aim of the current study was to unravel the molecular mechanisms involved in these beneficial metabolic effects of salsalate by treating mice with salsalate during and after development of high-fat diet-induced obesity. We found that salsalate attenuated and reversed high-fat diet-induced weight gain, in particular fat mass accumulation, improved glucose tolerance, and lowered plasma triglyceride levels. Mechanistically, salsalate selectively promoted the uptake of fatty acids from glycerol tri[(3)H]oleate-labeled lipoprotein-like emulsion particles by brown adipose tissue (BAT), decreased the intracellular lipid content in BAT, and increased rectal temperature, all pointing to more active BAT. The treatment of differentiated T37i brown adipocytes with salsalate increased uncoupled respiration. Moreover, salsalate upregulated Ucp1 expression and enhanced glycerol release, a dual effect that was abolished by the inhibition of cAMP-dependent protein kinase (PKA). In conclusion, salsalate activates BAT, presumably by directly activating brown adipocytes via the PKA pathway, suggesting a novel mechanism that may explain its beneficial metabolic effects in type 2 diabetes patients. Subject LifeMHR - Metabolic Health ResearchELSS - Earth, Life and Social SciencesBiomedical InnovationBiologyHealthy LivingSalicylic acid derivativeSalsalateAdministration and dosageAdverse effectsBrown adipose tissueDrug administrationDrug effectsFat intakeMetabolismMousePhysiologyTransgenic mouseAdipose Tissue, BrownAnimalsDietary FatsDrug Administration ScheduleGlucoseLipid MetabolismMaleMiceMice, TransgenicObesitySalicylatesWeight Gain To reference this document use: http://resolver.tudelft.nl/uuid:506d629c-6be0-4acc-96db-26e9cf076e55 DOI https://doi.org/10.2337/db14-1125 TNO identifier 526477 Source Diabetes, 64 (5), 1544-1554 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.