a Integrative Muscle Metabolism Laboratory, Human Performance Laboratory, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR 72701, USA.
b Exercise Muscle Biology Laboratory, Human Performance Laboratory, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR 72701, USA.
Appl Physiol Nutr Metab. 2017 Feb;42(2):148-156. doi: 10.1139/apnm-2016-0280. Epub 2016 Oct 12.
Obesity is a known risk factor for the development of hepatic disease; obesity-induced fatty liver can lead to inflammation, steatosis, and cirrhosis and is associated with degeneration of the mitochondria. Lifestyle interventions such as physical activity may ameliorate this condition. The purpose of this study was to investigate regulation of mitochondrial and autophagy quality control in liver following Western diet-induced obesity and voluntary physical activity. Eight-week-old C57BL/6J mice were fed a Western diet (WD) or normal chow (NC, control) for 4 weeks; afterwards, groups were divided into voluntary wheel running (VWR) or sedentary (SED) conditions for an additional 4 weeks. WD-SED animals had a median histology score of 2, whereas WD-VWR was not different from NC groups (median score 1). There was no difference in mRNA of inflammatory markers Il6 and Tnfa in WD animals. WD animals had 50% lower mitochondrial content (COX IV and Cytochrome C proteins), 50% lower Pgc1a mRNA content, and reduced content of mitochondrial fusion and fission markers. Markers of autophagy were increased in VWR animals, regardless of obesity, as measured by 50% greater LC3-II/I ratio and 40% lower p62 protein content. BNIP3 protein content was 30% less in WD animals compared with NC animals, regardless of physical activity. Diet-induced obesity results in derangements in mitochondrial quality control that appear to occur prior to the onset of hepatic inflammation. Moderate physical activity appears to enhance basal autophagy in the liver; increased autophagy may provide protection from hepatic fat accumulation.
肥胖是肝脏疾病发展的已知危险因素；肥胖引起的脂肪肝可导致炎症、脂肪变性和肝硬化，并与线粒体退化有关。生活方式干预，如体育活动，可能会改善这种情况。本研究的目的是研究西方饮食诱导肥胖和自愿体力活动后肝脏中线粒体和自噬质量控制的调节。8 周龄 C57BL/6J 小鼠用西方饮食（WD）或正常饲料（NC，对照）喂养 4 周；之后，将各组分为自愿轮跑（VWR）或久坐（SED）条件 4 周。WD-SED 动物的组织学评分中位数为 2，而 WD-VWR 与 NC 组无差异（中位数评分 1）。WD 动物的炎症标志物 Il6 和 Tnfa 的 mRNA 无差异。WD 动物的线粒体含量（COX IV 和细胞色素 C 蛋白）降低 50%，Pgc1a mRNA 含量降低 50%，线粒体融合和分裂标志物含量降低。无论肥胖与否，VWR 动物的自噬标志物增加，表现为 LC3-II/I 比值增加 50%，p62 蛋白含量降低 40%。与 NC 动物相比，WD 动物的 BNIP3 蛋白含量降低了 30%，无论是否进行体力活动。饮食诱导的肥胖导致线粒体质量控制的紊乱，这种紊乱似乎发生在肝炎症之前。适度的体力活动似乎增强了肝脏的基础自噬；增加的自噬可能提供了防止肝脂肪积累的保护。
