Peroxisomal gene and protein expression increase in response to a high-lipid challenge in human skeletal muscle

Peroxisomal gene and protein expression increase in response to a high-lipid challenge in human skeletal muscle
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DOI:
10.1016/j.metabol.2019.06.009
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发表时间:
2019-09-01
影响因子:
9.8
通讯作者:
Cortright, Ronald N.
Cortright, Ronald N.
中科院分区:
医学1区
文献类型:
--
作者:
Huang, Tai-Yu;Zheng, Donghai;Cortright, Ronald N.

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过氧酶体对脂质代谢是必不可少的,肝脏过氧酶体功能的紊乱会导致新生儿死亡。目的:我们假设和检验了过氧酶体基因/蛋白的表达和功能增加是对脂质供应过剩的一种适应性反应。材料和方法:收集了62例受试者的骨骼肌活组织标本,用于1)研究过氧酶体蛋白与细胞内脂质含量(IMLC)以及过氧酶体功能与IMLC之间的相关性,2)评估急性或7天高脂饮食(HFM)后过氧酶体基因的表达,而在人类组织中,衍生的初级肌管用于3)用高脂肪酸处理以诱导过氧化体适应。用生化分析和荧光染色检测IMLC。用Western blotting和实时荧光定量RT-PCR分别检测PMP70和PEX基因的表达。结果:1)禁食条件下,HSkM组织与线粒体功能呈显著正相关(P<0.05)。
Peroxisomes are essential for lipid metabolism and disruption of liver peroxisomal function results in neonatal death. Little is known about how peroxisomal content and activity respond to changes in the lipid environment in human skeletal muscle (HSkM).Aims: We hypothesized and tested that increased peroxisomal gene/protein expression and functionality occur in HSkM as an adaptive response to lipid oversupply.Materials and methods: HSkM biopsies, derived from a total of sixty-two subjects, were collected for 1) examining correlations between peroxisomal proteins and intramyocellular lipid content (IMLC) as well as between peroxisomal functionality and IMLC, 2) assessing peroxisomal gene expression in response to acute- or 7-day high fat meal (HFM), and in human tissue derived primary myotubes for 3) treating with high fatty acids to induce peroxisomal adaptions. IMLC were measured by both biochemical analyses and fluorescent staining. Peroxisomal membrane protein PMP70 and biogenesis gene (PEX) expression were assessed using western blotting and realtime qRT-PCR respectively. 1-C-14 radiolabeled lignocerate and palmitate oxidation assays were performed for peroxisomal and mitochondrial functionality respectively.Results: 1) Under fasting conditions, HSkMtissue demonstrated a significant correlation (P