Mechanisms of Insulin Resistance at the Crossroad of Obesity with Associated Metabolic Abnormalities and Cognitive Dysfunction.
Mechanisms of Insulin Resistance at the Crossroad of Obesity with Associated Metabolic Abnormalities and Cognitive Dysfunction.
复制标题
肥胖与相关代谢异常和认知功能障碍十字路口的胰岛素抵抗机制。
DOI：
10.3390/ijms22020546
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发表时间：
2021-01-07
影响因子：
5.6
通讯作者：
Weickert MO
中科院分区：
文献类型：
--
作者：
Barber TM;Kyrou I;Randeva HS;Weickert MO
肥胖通过胰岛素抵抗（IR）的发展介导其大部分直接医学后遗症。胰岛素的细胞效应通过两条主要的受体后途径发生，即磷脂酰肌醇 3 激酶 (PI3-K) 和丝裂原激活蛋白激酶 (MAP-K) 途径。肥胖相关的 IR 涉及赋予胰岛素代谢作用的 PI3-K 通路。许多复杂的致病途径将肥胖与IR的发展联系起来，包括慢性炎症、线粒体功能障碍（与活性氧和内质网应激的相关产生）、肠道微生物群失调和脂肪细胞外基质重塑。 IR本身在代谢功能障碍（包括高血压、血脂异常和血糖异常）的发展中起着关键作用。此外，IR 会促进与继发性高胰岛素血症相关的体重增加，从而导致 IR 恶化及其代谢后遗症的恶性循环。最终，IR 是 2 型糖尿病 (T2D) 和多囊卵巢综合征 (PCOS) 等肥胖相关疾病的基础。 IR 还通过代偿性高胰岛素血症对相对完整的 MAP-K 胰岛素通路（控制细胞生长过程和有丝分裂）的影响，导致许多与肥胖相关的恶性肿瘤。此外，近几十年来的新数据支持肥胖和 T2D 相关的中枢 IR 在认知功能障碍发展中的重要作用，包括对海马突触可塑性的影响。重要的是，IR在很大程度上可以通过优化生活方式因素来逆转，包括定期进行体力活动，避免久坐，改善饮食，包括增加纤维摄入量和充足的睡眠。 IR 处于肥胖与代谢和认知功能障碍之间的关键十字路口。鉴于 IR 在许多 21 世纪慢性疾病发病机制中的重要性及其显着的可逆性，我们所有人都拥抱并促进优化的生活方式，以改善大众未来的健康和福祉，这一点非常重要。
Obesity mediates most of its direct medical sequelae through the development of insulin resistance (IR). The cellular effects of insulin occur through two main postreceptor pathways that are the phosphatidylinositol 3-kinase (PI3-K) and the mitogen-activated protein kinase (MAP-K) pathways. Obesity-related IR implicates the PI3-K pathway that confers the metabolic effects of insulin. Numerous and complex pathogenic pathways link obesity with the development of IR, including chronic inflammation, mitochondrial dysfunction (with the associated production of reactive oxygen species and endoplasmic reticulum stress), gut microbiota dysbiosis and adipose extracellular matrix remodelling. IR itself plays a key role in the development of metabolic dysfunction, including hypertension, dyslipidaemia and dysglycaemia. Furthermore, IR promotes weight gain related to secondary hyperinsulinaemia, with a resulting vicious cycle of worsening IR and its metabolic sequelae. Ultimately, IR underlies obesity-related conditions such as type 2 diabetes mellitus (T2D) and polycystic ovary syndrome (PCOS). IR also underlies many obesity-related malignancies, through the effects of compensatory hyperinsulinaemia on the relatively intact MAP-K insulin pathway, which controls cellular growth processes and mitoses. Furthermore, the emergent data over recent decades support an important role of obesity- and T2D-related central IR in the development of cognitive dysfunction, including effects on hippocampal synaptic plasticity. Importantly, IR is largely reversible through the optimisation of lifestyle factors that include regular engagement in physical activity with the avoidance of sedentariness, improved diet including increased fibre intake and sleep sufficiency. IR lies at the key crossroad between obesity and both metabolic and cognitive dysfunction. Given the importance of IR in the pathogenesis of many 21st century chronic diseases and its eminent reversibility, it is important that we all embrace and facilitate optimised lifestyles to improve the future health and wellbeing of the populace.
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影响因子：
15.9
作者：
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通讯作者：
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影响因子：
3.2
作者：
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影响因子：
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作者：
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