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Adaptive immune cells shape obesity-associated type 2 diabetes mellitus and less prominent comorbidities
Nature Reviews Endocrinology ( IF 40.5 ) Pub Date : 2021-10-26 , DOI: 10.1038/s41574-021-00575-1
Sara SantaCruz-Calvo 1 , Leena Bharath 2 , Gabriella Pugh 3 , Lucia SantaCruz-Calvo 4 , Raji Rajesh Lenin 1 , Jenny Lutshumba 5 , Rui Liu 6 , Adam D Bachstetter 5 , Beibei Zhu 1 , Barbara S Nikolajczyk 1
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Obesity and type 2 diabetes mellitus (T2DM) are increasing in prevalence owing to decreases in physical activity levels and a shift to diets that include addictive and/or high-calorie foods. These changes are associated with the adoption of modern lifestyles and the presence of an obesogenic environment, which have resulted in alterations to metabolism, adaptive immunity and endocrine regulation. The size and quality of adipose tissue depots in obesity, including the adipose tissue immune compartment, are critical determinants of overall health. In obesity, chronic low-grade inflammation can occur in adipose tissue that can progress to systemic inflammation; this inflammation contributes to the development of insulin resistance, T2DM and other comorbidities. An improved understanding of adaptive immune cell dysregulation that occurs during obesity and its associated metabolic comorbidities, with an appreciation of sex differences, will be critical for repurposing or developing immunomodulatory therapies to treat obesity and/or T2DM-associated inflammation. This Review critically discusses how activation and metabolic reprogramming of lymphocytes, that is, T cells and B cells, triggers the onset, development and progression of obesity and T2DM. We also consider the role of immunity in under-appreciated comorbidities of obesity and/or T2DM, such as oral cavity inflammation, neuroinflammation in Alzheimer disease and gut microbiome dysbiosis. Finally, we discuss previous clinical trials of anti-inflammatory medications in T2DM and consider the path forward.



中文翻译:

适应性免疫细胞塑造与肥胖相关的 2 型糖尿病和不太显着的合并症

由于体力活动水平下降以及人们转向含有成瘾和/或高热量食物的饮食,肥胖和 2 型糖尿病 (T2DM) 的患病率正在增加。这些变化与现代生活方式的采用和肥胖环境的存在有关,导致新陈代谢、适应性免疫和内分泌调节的改变。肥胖症中脂肪组织沉积物的大小和质量,包括脂肪组织免疫区室,是整体健康的关键决定因素。在肥胖症中,脂肪组织中可能发生慢性低度炎症,并可能进展为全身炎症;这种炎症会导致胰岛素抵抗、T2DM 和其他合并症的发生。更好地了解肥胖期间发生的适应性免疫细胞失调及其相关代谢合并症,以及对性别差异的认识,对于重新利用或开发免疫调节疗法来治疗肥胖和/或 T2DM 相关炎症至关重要。这篇综述批判性地讨论了淋巴细胞(即 T 细胞和 B 细胞)的激活和代谢重编程如何触发肥胖和 T2DM 的发生、发展和进展。我们还考虑了免疫在未被充分认识的肥胖和/或 T2DM 合并症中的作用,例如口腔炎症、阿尔茨海默病中的神经炎症和肠道微生物群失调。最后,我们讨论了之前的 T2DM 抗炎药物临床试验并考虑了前进的道路。

更新日期:2021-10-26
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