NADPH oxidases in healthy white adipose tissue and in obesity: function, regulation, and clinical implications

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Obesity Pub Date : 2024-09-24 DOI:10.1002/oby.24113
François R. Jornayvaz, Karim Gariani, Emmanuel Somm, Vincent Jaquet, Karim Bouzakri, Ildiko Szanto
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Abstract

Reactive oxygen species, when produced in a controlled manner, are physiological modulators of healthy white adipose tissue (WAT) expansion and metabolic function. By contrast, unbridled production of oxidants is associated with pathological WAT expansion and the establishment of metabolic dysfunctions, most notably insulin resistance and type 2 diabetes mellitus. NADPH oxidases (NOXs) produce oxidants in an orderly fashion and are present in adipocytes and in other diverse WAT-constituent cell types. Recent studies have established several links between aberrant NOX-derived oxidant production, adiposity, and metabolic homeostasis. The objective of this review is to highlight the physiological roles attributed to diverse NOX isoforms in healthy WAT and summarize current knowledge of the metabolic consequences related to perturbations in their adequate oxidant production. We detail WAT-related alterations in preclinical investigations conducted in NOX-deficient murine models. In addition, we review clinical studies that have employed NOX inhibitors and currently available data related to human NOX mutations in metabolic disturbances. Future investigations aimed at understanding the integration of NOX-derived oxidants in the regulation of the WAT cellular redox network are essential for designing successful redox-related precision therapies to curb obesity and attenuate obesity-associated metabolic pathologies.

Abstract Image

健康白色脂肪组织和肥胖症中的 NADPH 氧化酶:功能、调节和临床意义。
活性氧以可控方式产生时,是健康白色脂肪组织(WAT)扩张和新陈代谢功能的生理调节剂。与此相反,氧化剂的无节制产生与病理性白脂肪组织扩张和代谢功能障碍的形成有关,其中最明显的是胰岛素抵抗和 2 型糖尿病。NADPH 氧化酶(NOXs)以有序的方式产生氧化剂,存在于脂肪细胞和其他多种组成脂肪细胞的细胞类型中。最近的研究发现,NOX 衍生氧化剂的异常产生、脂肪和代谢平衡之间存在着多种联系。本综述旨在强调不同 NOX 同工酶在健康 WAT 中的生理作用,并总结目前与 NOX 氧化剂产生相关的代谢后果的知识。我们详细介绍了在 NOX 缺陷小鼠模型中进行的临床前研究发现的与 WAT 相关的改变。此外,我们还回顾了采用 NOX 抑制剂进行的临床研究,以及与代谢紊乱中的人类 NOX 突变有关的现有数据。未来的研究旨在了解 NOX 衍生氧化剂在调节 WAT 细胞氧化还原网络中的整合作用,这对设计成功的氧化还原相关精准疗法以遏制肥胖和减轻肥胖相关代谢病症至关重要。
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来源期刊
Obesity
Obesity 医学-内分泌学与代谢
CiteScore
11.70
自引率
1.40%
发文量
261
审稿时长
2-4 weeks
期刊介绍: Obesity is the official journal of The Obesity Society and is the premier source of information for increasing knowledge, fostering translational research from basic to population science, and promoting better treatment for people with obesity. Obesity publishes important peer-reviewed research and cutting-edge reviews, commentaries, and public health and medical developments.
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