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肥胖相关炎症中 T 细胞代谢的解读。

T-cell Metabolism as Interpreted in Obesity-associated Inflammation.

机构信息

Department of Nutrition and Public Health, Merrimack College, North Andover, MA 01845, USA.

Departments of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536, USA.

出版信息

Endocrinology. 2022 Oct 1;163(10). doi: 10.1210/endocr/bqac124.

Abstract

The appreciation of metabolic regulation of T-cell function has exploded over the past decade, as has our understanding of how inflammation fuels comorbidities of obesity, including type 2 diabetes. The likelihood that obesity fundamentally alters T-cell metabolism and thus chronic obesity-associated inflammation is high, but studies testing causal relationships remain underrepresented. We searched PubMed for key words including mitochondria, obesity, T cell, type 2 diabetes, cristae, fission, fusion, redox, and reactive oxygen species to identify foundational and more recent studies that address these topics or cite foundational work. We investigated primary papers cited by reviews found in these searches and highlighted recent work with >100 citations to illustrate the state of the art in understanding mechanisms that control metabolism and thus function of various T-cell subsets in obesity. However, "popularity" of a paper over the first 5 years after publication cannot assess long-term impact; thus, some likely important work with fewer citations is also highlighted. We feature studies of human cells, supplementing with studies from animal models that suggest future directions for human cell research. This approach identified gaps in the literature that will need to be filled before we can estimate efficacy of mitochondria-targeted drugs in clinical trials to alleviate pathogenesis of obesity-associated inflammation.

摘要

过去十年中,人们对 T 细胞功能代谢调控的认识有了突飞猛进的发展,对炎症如何引发肥胖的合并症(包括 2 型糖尿病)的认识也有了深入的了解。肥胖极有可能从根本上改变 T 细胞的代谢,从而导致慢性肥胖相关炎症,这是很有可能的,但仍缺乏相关因果关系研究。我们在 PubMed 中搜索了包括线粒体、肥胖、T 细胞、2 型糖尿病、嵴、裂变、融合、氧化还原和活性氧在内的关键词,以确定涉及这些主题或引用基础工作的基础和最新研究。我们调查了这些搜索中综述引用的主要论文,并强调了最近有超过 100 次引用的工作,以说明控制代谢和因此控制肥胖中各种 T 细胞亚群功能的机制的最新进展。然而,一篇论文在发表后的前 5 年内的“流行度”并不能评估其长期影响;因此,一些引用较少但可能很重要的工作也被突出显示。我们介绍了人类细胞的研究,并补充了来自动物模型的研究,这些研究为人类细胞研究提供了未来的方向。这种方法确定了文献中的空白,在我们能够估计靶向线粒体的药物在临床试验中缓解肥胖相关炎症发病机制的疗效之前,这些空白需要填补。

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