高脂肪日粮引起肥胖和代谢综合征的分子机制.pptxVIP

Molecular Mechanisms of High Fat Diet-Induced Obesity and Metabolic Syndromes高脂肪日粮引起肥胖和代谢综合症的分子机制;Modern high fat diet (HFD) and overfeeding;HFD lead to obesity;How HFD induces obesity?;Systemic energy surplus leads to obesity;Storage of nutrient-derived energy surplus;Adipocytes store HFD-derived “fat”;HFD leads to adipocyte hypertrophy;HFD also leads to adipocyte hyperplasia;HFD further changes the color of fat;Three types of adipocytes：origin， function;White, beige and brown fat have distinct role in energy balance;HFD leads to whitening of fat ;抑制Notch信号通路促进白色脂肪组织的棕色化并减轻肥胖;Notch Signaling Transduction;HFD activates Notch signaling in adipose;Notch is inversely correlated to brown fat gene expression;Adipose-specific ablation of Notch 1 in mice;;Notch 1 cKO leads to browning and reduce adiposity;Notch 1 cKO increases brown/beige gene expression;Rbpjk cKO in adipose also lead to browning;Notch1 cKO boosts cold induced browning;Notch cKO improves glucose metabolism;Notch1 cKO increases metabolic rate;Notch1 cKO protects mice against HFD-induced obesity;Summary-1;Notch inhibition upregulates BAT genes in cultured white adipocytes;Gene expression of Notch targets (left) and BAT-related genes (middle) and protein levels of N1ICD, Ucp1 and Pgc1-α (right) in cultured white adipocytes from MT mice treated with DAPT during induction and differentiation.;Notch inhibits BAT genes cell- autonomously;Gene expression of WT preadipocytes after transfection with Hey1 (d) or Hes1 (e) plasmids;Hes1 inhibits Pgc1α and Prdm16 gene transcription;Summary-2;Can Notch inhibitor ameliorate obesity in Ob/Ob mice-a model of HFD-induced obesity？;Notch inhibitor blocks body weight gain of Ob mice;Notch inhibitor reduces adiposity in Ob mice;Notch inhibitor ameliorates glucose metabolism in Ob mice;Summary-3;Thank you for your attention!