Department of Pharmaceutical Sciences, University of Perugia, 06126 Perugia, Italy.
Centro Servizi Metrologici e Tecnologici Avanzati (CeSMA), Complesso Universitario di Monte Sant'Angelo, Via Cinthia 21, 80126 Naples, Italy.
Int J Mol Sci. 2023 Feb 3;24(3):2967. doi: 10.3390/ijms24032967.
Obesity is considered an epidemic disorder, due to an imbalance between energy consumption and metabolizable energy intake. This balance is increasingly disrupted during normal aging processes due to the progressive impairment of mechanisms that normally control energy homeostasis. Obesity is triggered by an excessive lipid depots but reflects systemic inflammation along with large adipocytes secreting proinflammatory adipokines, an increase of the free fatty acids levels in the bloodstream, and ectopic lipid accumulation. Hepatic fat accumulation is the most common cause of chronic liver disease, characterized by mitochondrial dysfunction with a consequent impaired fat metabolism and increased oxidative stress. Therefore, mitochondrial dysfunction is associated to hepatic lipid accumulation and related complications. In this study, we assessed the crosstalk between adipose tissue and liver, analyzing the time-course of changes in hepatic mitochondrial fatty acid oxidation capacity versus fatty acid storage, focusing on the contribution of adipose tissue inflammation to hepatic lipid accumulation, using a rodent model of high fat diet-induced obesity. Our results demonstrate that both high-fat diet-induced obesity and aging induce dysregulation of adipose tissue function and similar metabolic alterations mediated by mitochondrial function impairment and altered inflammatory profile. The high fat diet-induced obesity anticipates and exacerbates liver mitochondrial dysfunction that occurs with aging processes.
肥胖被认为是一种流行疾病,是由于能量消耗和可代谢能量摄入之间的失衡造成的。在正常衰老过程中,这种平衡由于正常控制能量稳态的机制逐渐受损而越来越被打破。肥胖是由过多的脂质储存引起的,但反映了全身性炎症以及大脂肪细胞分泌促炎脂肪因子,血液中游离脂肪酸水平的增加,和异位脂质积累。肝脂肪堆积是慢性肝病最常见的原因,其特征为线粒体功能障碍,导致脂肪代谢受损和氧化应激增加。因此,线粒体功能障碍与肝脂质堆积和相关并发症有关。在这项研究中,我们评估了脂肪组织和肝脏之间的串扰,分析了肝线粒体脂肪酸氧化能力与脂肪酸储存变化的时间进程,重点关注脂肪组织炎症对肝脂质堆积的贡献,使用高脂肪饮食诱导肥胖的啮齿动物模型。我们的结果表明,高脂肪饮食诱导的肥胖和衰老都会导致脂肪组织功能失调和类似的代谢改变,这些改变是由线粒体功能障碍和炎症特征改变介导的。高脂肪饮食诱导的肥胖会提前并加重与衰老过程相关的肝线粒体功能障碍。