Xie Wei-Dong, Wang Hua, Zhang Jin-Fang, Li Jian-Na, Can Yi, Qing Lv, Kung Hsiang-Fu, Zhang Ya-Ou
Life Science Division, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055;
Exp Ther Med. 2011 Mar;2(2):309-315. doi: 10.3892/etm.2011.208. Epub 2011 Jan 20.
This study aimed to investigate the potential mechanisms of natural resistance to high-fat diet-induced obesity. Four-week-old C57BL/6 mice were fed a high-fat diet for 6 weeks and were then designated as high-fat diet-fed obesity-prone (HOP) and obesity-resistant (HOR) animals. Their blood biochemistry was evaluated, and visceral adipose tissue samples were subjected to proteomic, Western blot and quantitative real-time PCR (q-PCR) analyses. The HOR mice showed reduced visceral fat weight and size, as well as lowered serum lipid and leptin levels. Proteomic analysis showed that enoyl coenzyme A hydratase 1, peroxisomal (Ech1) expression was significantly increased in their visceral adipose tissues. Moreover, other proteins, such as α-tropomyosin, myosin light chain, urine-nucleoside phosphorylase and transgelin, were also significantly increased. Furthermore, q-PCR analysis showed that the expression of acyl-CoA oxidase 1 palmitoyl, enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase and 3-oxoacyl-CoA thiolase responsible for peroxisomal β-oxidation was also up-regulated in the visceral adipose tissues of the HOR mice. The expression of peroxisome proliferator-activated receptor α (PPARα) was increased in the HOR mice as shown by Western blot analysis. Obesity-resistant animals show enhanced peroxisomal β-oxidation metabolism and reduced fat accumulation in visceral adipose tissues by up-regulating the expression of Ech1, peroxisomal or other related peroxisomal β-oxidation marker genes, which may be driven or enhanced by the up-regulation of the expression of PPARα. However, further validation in future studies is required.
本研究旨在探究对高脂饮食诱导的肥胖产生天然抗性的潜在机制。将4周龄的C57BL/6小鼠喂食高脂饮食6周,然后将其分为高脂饮食诱导的肥胖易感(HOP)和肥胖抗性(HOR)动物。评估它们的血液生化指标,并对内脏脂肪组织样本进行蛋白质组学、蛋白质印迹和定量实时PCR(q-PCR)分析。HOR小鼠的内脏脂肪重量和大小降低,血清脂质和瘦素水平也降低。蛋白质组学分析表明,过氧化物酶体烯酰辅酶A水合酶1(Ech1)在内脏脂肪组织中的表达显著增加。此外,其他蛋白质,如α-原肌球蛋白、肌球蛋白轻链、尿核苷磷酸化酶和原肌球蛋白也显著增加。此外,q-PCR分析表明,负责过氧化物酶体β-氧化的酰基辅酶A氧化酶1棕榈酰、烯酰辅酶A水合酶/3-羟基酰基辅酶A脱氢酶和3-氧代酰基辅酶A硫解酶在内脏脂肪组织中的表达也上调。蛋白质印迹分析显示,HOR小鼠中过氧化物酶体增殖物激活受体α(PPARα)的表达增加。肥胖抗性动物通过上调Ech1、过氧化物酶体或其他相关过氧化物酶体β-氧化标记基因的表达,增强了过氧化物酶体β-氧化代谢,减少了内脏脂肪组织中的脂肪积累,这可能是由PPARα表达的上调所驱动或增强的。然而,未来的研究需要进一步验证。