Table_2_Links Between Obesity-Induced Brain Insulin Resistance, Brain Mitochondrial Dysfunction, and Dementia.DOC

It is widely recognized that obesity and associated metabolic changes are considered a risk factor to age-associated cognitive decline. Inflammation and increased oxidative stress in peripheral areas, following obesity, are patently the major contributory factors to the degree of the severity of brain insulin resistance as well as the progression of cognitive impairment in the obese condition. Numerous studies have demonstrated that the alterations in brain mitochondria, including both functional and morphological changes, occurred following obesity. Several studies also suggested that brain mitochondrial dysfunction may be one of underlying mechanism contributing to brain insulin resistance and cognitive impairment in the obese condition. Thus, this review aimed to comprehensively summarize and discuss the current evidence from various in vitro, in vivo, and clinical studies that are associated with obesity, brain insulin resistance, brain mitochondrial dysfunction, and cognition. Contradictory findings and the mechanistic insights about the roles of obesity, brain insulin resistance, and brain mitochondrial dysfunction on cognition are also presented and discussed. In addition, the potential therapies for obese-insulin resistance are reported as the therapeutic strategies which exert the neuroprotective effects in the obese-insulin resistant condition.

众所周知，肥胖及其伴随的代谢改变是年龄相关性认知衰退的公认危险因素。肥胖诱导的外周炎症与氧化应激加剧，显然是加剧肥胖状态下大脑胰岛素抵抗（brain insulin resistance）严重程度、推动认知损伤进展的核心诱因。诸多研究证实，肥胖可引发大脑线粒体出现功能与形态学层面的双重异常改变。另有多项研究表明，大脑线粒体功能障碍（brain mitochondrial dysfunction）或许是肥胖状态下大脑胰岛素抵抗与认知损伤的潜在发病机制之一。
据此，本综述旨在全面梳理并讨论当前来自各类体外（in vitro）、体内（in vivo）及临床研究的相关证据，这些研究均围绕肥胖、大脑胰岛素抵抗、大脑线粒体功能障碍与认知功能展开。本文还将呈现并探讨关于肥胖、大脑胰岛素抵抗及大脑线粒体功能障碍对认知功能影响的矛盾性研究结果与机制阐释。此外，本文还将报道针对肥胖-胰岛素抵抗的潜在治疗手段，这类治疗策略可在肥胖胰岛素抵抗状态下发挥神经保护作用。