了解脂肪组织巨噬细胞和生命早期代谢编程的关键问题和差距。

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Kaitlyn B Hill, Gregory P Mullen, Prabhakara R Nagareddy, Kurt A Zimmerman, Michael C Rudolph
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引用次数: 0

摘要

全球肥胖症的流行及其相关的并发症和早期死亡风险的增加,突出表明我们迫切需要加强对这一复杂疾病起源的了解。人们越来越清楚地认识到,新陈代谢在生命早期就已形成,而新陈代谢的形成会对健康产生终身影响。作为对生命早期刺激敏感的重要代谢器官,脂肪组织(AT)的正常发育对终生能量平衡至关重要。生命早期的营养物质,尤其是脂肪酸(FA),会对脂肪组织的发育产生重要影响,并塑造其功能和新陈代谢。人们越来越感兴趣的是,在产前和产后发育过程中,脂肪分解代谢过程中暴露于促炎性欧米伽-6(n6)和抗炎性欧米伽-3(n3)脂肪酸的动态反应。在美国母体饮食中,由于 n6-FA 的流行,"促炎 "n6-与 "抗炎 "n3-FA 的比例急剧上升。值得注意的是,脂肪间质巨噬细胞(ATM)是脂肪基质细胞中的一个重要群体,不仅在脂肪间质的形成和维持中发挥着重要作用,而且还是细胞间脂质和细胞因子信号转导的关键介质。尽管 ATM 和免疫代谢领域进展迅速,但研究主要集中在对肥胖饮食和成年期的反应上。因此,在确定促进新陈代谢健康的机制方面还存在很大差距,尤其是在建立 ATM 生理过程中的脂质暴露方面。我们的综述强调了目前对 ATM 多样性的理解、它们在 AT 中的关键作用、它们在生命早期代谢编程中的潜在作用以及对代谢和健康的广泛影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Key questions and gaps in understanding adipose tissue macrophages and early-life metabolic programming.

The global obesity epidemic, with its associated comorbidities and increased risk of early mortality, underscores the urgent need for enhancing our understanding of the origins of this complex disease. It is increasingly clear that metabolism is programmed early in life and that metabolic programming can have life-long health consequences. As a critical metabolic organ sensitive to early-life stimuli, proper development of adipose tissue (AT) is crucial for life-long energy homeostasis. Early-life nutrients, especially fatty acids (FAs), significantly influence the programming of AT and shape its function and metabolism. Of growing interest are the dynamic responses during pre- and postnatal development to proinflammatory omega-6 (n6) and anti-inflammatory omega-3 (n3) FA exposures in AT. In the US maternal diet, the ratio of "pro-inflammatory" n6- to "anti-inflammatory" n3-FAs has grown dramatically due to the greater prevalence of n6-FAs. Notably, AT macrophages (ATMs) form a significant population within adipose stromal cells, playing not only an instrumental role in AT formation and maintenance but also acting as key mediators of cell-to-cell lipid and cytokine signaling. Despite rapid advances in ATM and immunometabolism fields, research has focused on responses to obesogenic diets and during adulthood. Consequently, there is a significant gap in identifying the mechanisms contributing metabolic health, especially regarding lipid exposures during the establishment of ATM physiology. Our review highlights the current understanding of ATM diversity, their critical role in AT, their potential role in early-life metabolic programming, and the broader implications for metabolism and health.

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来源期刊
CiteScore
9.80
自引率
0.00%
发文量
98
审稿时长
1 months
期刊介绍: The American Journal of Physiology-Endocrinology and Metabolism publishes original, mechanistic studies on the physiology of endocrine and metabolic systems. Physiological, cellular, and molecular studies in whole animals or humans will be considered. Specific themes include, but are not limited to, mechanisms of hormone and growth factor action; hormonal and nutritional regulation of metabolism, inflammation, microbiome and energy balance; integrative organ cross talk; paracrine and autocrine control of endocrine cells; function and activation of hormone receptors; endocrine or metabolic control of channels, transporters, and membrane function; temporal analysis of hormone secretion and metabolism; and mathematical/kinetic modeling of metabolism. Novel molecular, immunological, or biophysical studies of hormone action are also welcome.
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