Salsalate activates brown adipose tissue in mice
| Jazyk: | angličtina |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Male
Fat intake Mouse Physiology Biomedical Innovation Administration and dosage Brown adipose tissue Weight Gain Drug Administration Schedule Transgenic Mice Life Salsalate Transgenic mouse Animals Obesity Life and Social Sciences Biology Drug effects Adverse effects Drug administration Brown ELSS - Earth Lipid Metabolism Dietary Fats Salicylates Metabolism Glucose Adipose Tissue Salicylic acid derivative MHR - Metabolic Health Research Healthy Living |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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