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Salsalate activates brown adipose tissue in mice.
MedLine Citation:
PMID:  25475439     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Salsalate improves glucose intolerance and dyslipidemia in type 2 diabetes patients, but the mechanism is still unknown. The aim of the present 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 (TG) 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. Treatment of differentiated T37i brown adipocytes with salsalate increased uncoupled respiration in cells. Moreover, salsalate upregulated Ucp1 expression and enhanced glycerol release, a dual effect that was abolished by inhibition of protein kinase A (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.
Authors:
Andrea D van Dam; Kimberly J Nahon; Sander Kooijman; Susan M van den Berg; Anish A Kanhai; Takuya Kikuchi; Mattijs M Heemskerk; Vanessa van Harmelen; Marc Lombès; Anita M van den Hoek; Menno P J de Winther; Esther Lutgens; Bruno Guigas; Patrick C N Rensen; Mariëtte R Boon
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-12-4
Journal Detail:
Title:  Diabetes     Volume:  -     ISSN:  1939-327X     ISO Abbreviation:  Diabetes     Publication Date:  2014 Dec 
Date Detail:
Created Date:  2014-12-5     Completed Date:  -     Revised Date:  2014-12-6    
Medline Journal Info:
Nlm Unique ID:  0372763     Medline TA:  Diabetes     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
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