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烟酰胺核糖可将人类原代白色脂肪细胞的分化转变为米色脂肪细胞,通过激活SIRT1和产生线粒体衍生的活性物质来影响底物偏好和解偶联呼吸。

Nicotinamide-riboside shifts the differentiation of human primary white adipocytes to beige adipocytes impacting substrate preference and uncoupling respiration through SIRT1 activation and mitochondria-derived reactive species production.

作者信息

Nagy Lilla, Rauch Boglárka, Szerafin Tamás, Uray Karen, Tóth Attila, Bai Péter

机构信息

Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

Department of Cardiology and Heart Surgery, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

出版信息

Front Cell Dev Biol. 2022 Aug 22;10:979330. doi: 10.3389/fcell.2022.979330. eCollection 2022.

DOI:10.3389/fcell.2022.979330
PMID:36072335
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9441796/
Abstract

Beige adipocytes play key roles in organismal energy and metabolic balance. In this study, we assessed whether the supplementation of human white adipocytes, differentiated from human adipose tissue-derived stem cells, with nicotinamide riboside (NR), a potent NAD + precursor, can shift differentiation to beige adipocytes (beiging). NR induced mitochondrial biogenesis and the expression of beige markers (TBX1 and UCP1) in white adipocytes demonstrating that NR can declutch beiging. NR did not induce PARP activity but supported SIRT1 induction, which plays a key role in beiging. NR induced etomoxir-resistant respiration, suggesting increases in the oxidation of carbohydrates, carbohydrate breakdown products, or amino acids. Furthermore, NR boosted oligomycin-resistant respiration corresponding to uncoupled respiration. Enhanced etomoxir and oligomycin-resistant respiration were dependent on mitochondrial reactive-species production. Taken together, NR supplementation can induce beiging and uncoupled respiration, which are beneficial for combatting metabolic diseases.

摘要

米色脂肪细胞在机体能量和代谢平衡中发挥着关键作用。在本研究中,我们评估了用烟酰胺核糖(NR)(一种有效的NAD⁺前体)补充从人脂肪组织衍生干细胞分化而来的人白色脂肪细胞,是否能使分化转变为米色脂肪细胞(米色化)。NR诱导白色脂肪细胞中线粒体生物发生和米色标志物(TBX1和UCP1)的表达,表明NR可引发米色化。NR未诱导PARP活性,但支持SIRT1诱导,而SIRT1在米色化中起关键作用。NR诱导依托莫昔芬抗性呼吸,提示碳水化合物、碳水化合物分解产物或氨基酸的氧化增加。此外,NR增强了与解偶联呼吸相对应的寡霉素抗性呼吸。增强的依托莫昔芬和寡霉素抗性呼吸依赖于线粒体活性氧的产生。综上所述,补充NR可诱导米色化和解偶联呼吸,这对对抗代谢疾病有益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b623/9441796/40c543239aca/fcell-10-979330-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b623/9441796/40c543239aca/fcell-10-979330-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b623/9441796/40c543239aca/fcell-10-979330-g001.jpg

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本文引用的文献

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Boosting NAD+ blunts TLR4-induced type I IFN in control and systemic lupus erythematosus monocytes.
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The Crosstalk between Gut Microbiota and White Adipose Tissue Mitochondria in Obesity.肠道微生物群与肥胖症白色脂肪组织线粒体的串扰。
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