Sirt1 decreased adipose inflammation by interacting with Akt2 and inhibiting mTOR/S6K1 pathway in mice.
Sirtuin type 1 (Sirt1) and protein kinase B (Akt2) are associated with development of obesity and inflammation, but the molecular mechanisms of Sirt1 and Akt2 interaction on adipose inflammation remain unclear. To explore these mechanisms, a mouse model was used. Mice were fed with a high-fat diet (HFD) for 8 weeks, with interventions of resveratrol (RES) or nicotinamide (NAM) during the last 15 days. The HFD reduced Sirt1 mRNA in adipose tissue and elevated interleukin-6 (IL-6) expression. RES reduced the adipose tissue weight, increased the Sirt1 mRNA level, and reduced both mRNA and protein levels of IL-6, MCP-1, inducible nitric oxide synthase, and TNF-α by inhibiting phosphorylation of Akt2 in adipose tissue. Additionally, macrophage type I marker genes were reduced while macrophage type II marker genes were elevated by RES addition. Moreover, activation of Akt2 signal by using insulin significantly blunted the inhibitory effect of RES on adipose inflammation. Immunoprecipitation assay demonstrated that RES enhances the protein-protein interaction between Sirt1 and Akt2, but NAM inhibits this interaction. Furthermore, Sirt1 significantly reduced the levels of raptor and inactivated mammalian target of rapamycin (mTOR)C1 signal by interacting with Akt2, and confirmed that RES attenuated adipose inflammation by inhibiting the mTOR/S6K1 pathway via rapamycin.
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
Zhenjiang
Z
Liu
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
Lu
L
Gan
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
Guannv
G
Liu
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
Yizhe
Y
Chen
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
Tianjiao
T
Wu
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
Fei
F
Feng
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China sunchao2775@163.com.
Chao
C
Sun
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology; D002478:Cells, Cultured; D059305:Diet, High-Fat / Q000009:adverse effects; D004789:Enzyme Activation / Q000187:drug effects; D007249:Inflammation / Q000201:enzymology; D007328:Insulin / Q000502:physiology; D008297:Male; D051379:Mice; D009536:Niacinamide / Q000494:pharmacology; D009765:Obesity / Q000201:enzymology / Q000209:etiology / Q000276:immunology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D000076223:Regulatory-Associated Protein of mTOR; D000077185:Resveratrol; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000502:physiology*; D013267:Stilbenes / Q000494:pharmacology; D050151:Subcutaneous Fat / Q000201:enzymology* / Q000276:immunology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D019440:Anti-Obesity Agents; D007328:Insulin; D000076223:Regulatory-Associated Protein of mTOR; C540162:Rptor protein, mouse; D013267:Stilbenes; D009536:Niacinamide; C546843:mTOR protein, mouse; C494922:Akt2 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C512964:Rps6ka1 protein, mouse; D058570:TOR Serine-Threonine Kinases; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D000077185:Resveratrol
mammalian target of rapamycin C1; mammalian target of rapamycin/S6 kinase 1; protein kinase B; sirtuin type 1