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
Life
MHR - Metabolic Health Research
ELSS - Earth, Life and Social Sciences
Biomedical Innovation
Biology
Healthy Living
Salicylic acid derivative
Salsalate
Administration and dosage
Adverse effects
Brown adipose tissue
Drug administration
Drug effects
Fat intake
Metabolism
Mouse
Physiology
Transgenic mouse
Adipose Tissue, Brown
Animals
Dietary Fats
Drug Administration Schedule
Glucose
Lipid Metabolism
Male
Mice
Mice, Transgenic
Obesity
Salicylates
Weight 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