Feillet-Coudray Christine, Fouret Gilles, Vigor Claire, Bonafos Béatrice, Jover Bernard, Blachnio-Zabielska Agnieszka, Rieusset Jennifer, Casas François, Gaillet Sylvie, Landrier Jean Francois, Durand Thierry, Coudray Charles
DMEM (Dynamique Musculaire & Métabolisme) INRA, University of Montpellier, 2 Place Viala, 34060, Montpellier, France.
Institut des Biomolécules Max Mousseron, IBMM, University of Montpellier, CNRS, ENSCM, 15 Avenue Charles Flahault, 34090, Montpellier, France.
Lipids. 2019 Jan;54(1):81-97. doi: 10.1002/lipd.12128. Epub 2019 Feb 14.
Inflammation and oxidative stress are thought to be involved in, or associated with, the development of obesity, dyslipidemia, hepatic steatosis, and insulin resistance. This work was designed to determine the evolution of inflammation and oxidative stress during onset and progression of hepatic steatosis and glucose intolerance. Seventy-five male Wistar rats were divided to control and high-fat high-fructose (HFHFr) groups. A subgroup of each group was sacrificed at 4, 8, 12, 16, and 20 weeks. HFHFr-fed rats exhibited overweight, glucose intolerance, and hepatic steatosis with increased contents of hepatic diacylglycerols and ceramides. The HFHFr diet increased hepatic interleukin 6 (IL-6) protein and adipose tissue CCL5 gene expression and hepatic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity but not mitochondrial reactive oxygen species (ROS) production. The HFHFr diet decreased plasma and liver levels of isoprostanoid metabolites as well as plasma thiobarbituric acid-reactive substance (TBARS) levels. Hepatic glutathione content was decreased with a moderate decrease in superoxide dismutase (SOD) and glutathione peroxidase (GPx) with the HFHFr diet. Overall, HFHFr diet led to hepatic lipid accumulation and glucose intolerance, which were accompanied by only moderate inflammation and oxidative stress. Most of these changes occurred at the same time and as early as 8 or 12 weeks of diet treatment. This implies that oxidative stress may be the result, not the cause, of these metabolic alterations, and suggests that marked hepatic oxidative stress should probably occur at the end of the steatotic stage to result in frank insulin resistance and steatohepatitis. These findings need to be further evaluated in other animal species as well as in human studies.
炎症和氧化应激被认为与肥胖、血脂异常、肝脂肪变性和胰岛素抵抗的发生或发展有关。这项研究旨在确定肝脂肪变性和葡萄糖不耐受发生及进展过程中炎症和氧化应激的演变情况。将75只雄性Wistar大鼠分为对照组和高脂高果糖（HFHFr）组。每组的一个亚组在4、8、12、16和20周时处死。喂食HFHFr的大鼠出现超重、葡萄糖不耐受和肝脂肪变性，同时肝二酰甘油和神经酰胺含量增加。HFHFr饮食增加了肝脏白细胞介素6（IL-6）蛋白和脂肪组织CCL5基因表达以及肝脏烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶活性，但未增加线粒体活性氧（ROS）的产生。HFHFr饮食降低了血浆和肝脏中异前列腺素代谢产物水平以及血浆硫代巴比妥酸反应性物质（TBARS）水平。HFHFr饮食使肝脏谷胱甘肽含量降低，同时超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPx）略有下降。总体而言，HFHFr饮食导致肝脏脂质蓄积和葡萄糖不耐受，同时仅伴有适度的炎症和氧化应激。这些变化大多同时发生，且早在饮食治疗的8或12周时就已出现。这意味着氧化应激可能是这些代谢改变的结果而非原因，并表明在脂肪变性阶段末期可能会出现明显的肝脏氧化应激，从而导致明显的胰岛素抵抗和脂肪性肝炎。这些发现需要在其他动物物种以及人体研究中进一步评估。
