高脂肪日粮引起肥胖和代谢综合征的分子机制ppt课件.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 Shihuan Kuang, Ph.D. Associate Professor Purdue University, USA Modern high fat diet (HFD) and overfeeding HFD lead to obesity Gesta et al., 2007 How HFD induces obesity? Systemic energy surplus leads to obesity Patrick Seale et al., 2009 Storage of nutrient-derived energy surplus 营养物质 消化系统 脑 肝 胰腺 葡萄糖 糖原 肌肉 甘油三脂 胰岛素 脂肪组织 脂肪因子 游离氨基酸 葡萄糖 Adipocytes store HFD-derived “fat” HFD leads to adipocyte hypertrophy TISSUE TURNS BAD Cell overloaded with lipid rapidly outgrow oxygen supply, leading to cell death and inflammation. HFD also leads to adipocyte hyperplasia HFD further changes the color of fat Three types of adipocytes：origin， function Brown adipose tissue White adipose tissue Hibernating Organ Energy storage Organ Brown and Beige adipose: Small lipid droplets UCP1 expression Dense mitochondria Burn lipids into heat More energy expenditure Harms Seale, 2013 Cannon Nedergaard， 2012 White, beige and brown fat have distinct role in energy balance Patrick Seale et al., 2009 HFD leads to whitening of fat What’s the underlying signaling mechanism? Bartelt Heeren, 2014 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 Grabher et al., 2006 HFD activates Notch signaling in adipose Receptors Ligands SD-standard diet N1ICD-activated Notch 1 Notch is inversely correlated to brown fat gene expression Adipose-specific ablation of Notch 1 in mice 脂肪结合蛋白4的表达量标志着白色和棕色脂肪组织中原始脂肪细胞的数量 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 4℃ Notch cKO improves glucose metabolism GTT, glucose tolerance test； ITT, insulin tolerance test Notch1 cKO increases metabolic rate Notch1 cKO protects mice against HFD-induced obesity Summary-1 HDF activates Notch signaling in white adipose tissues Notch is inversely correlated with brown fat gene expression G