Functional thermogenic beige adipogenesis is inducible in human neck fat.
Functional thermogenic beige adipogenesis is inducible in human neck fat.
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DOI：
10.1038/ijo.2013.82
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发表时间：
2014-03
期刊：
影响因子：
--
通讯作者：
Celi FS
中科院分区：
文献类型：
--
作者：
Lee P;Werner CD;Kebebew E;Celi FS
最近的研究表明，人类颈部棕色脂肪组织（BAT）由“棕色脂肪细胞（BA）样”或米色脂肪细胞组成。然而，人们对它们的产热功能知之甚少。在米色脂肪细胞转录组中，成纤维细胞生长因子-21 （FGF21）是一个基因，其蛋白产物作为脂肪因子，调节动物冷诱导的产热作用。在这里，我们探讨了(i)来源于人类颈部脂肪的米色脂肪细胞的成脂潜能、产热功能和FGF21分泌能力，以及（ii） FGF21在调节脂肪生物能量学中的作用。从人颈部脂肪中分离的祖细胞分化为ba样或白色脂肪细胞（WA）表型的脂肪细胞。采用酶联免疫吸附法检测FGF21的分泌。Real-time PCR/western blotting检测细胞mRNA/蛋白水平。细胞外通量生物分析仪用于定量脂肪细胞耗氧量和脂肪酸氧化。用红外热像仪测量脂肪细胞产热。在激素调控下，人颈部原代前脂肪细胞在基因/蛋白和功能水平上分化为ba样或WA表型的脂肪细胞。BA样细胞表达米色，但不表达经典的BA标记物。在BA分化过程中，FGF21基因的表达和分泌增加，并在去甲肾上腺素暴露（体外冷模拟）后增强。分化的WA表达介导FGF21作用的关键辅助因子β-klotho。用FGF21处理WA诱导UCP1表达，增加耗氧量、呼吸解偶联、去甲肾上腺素介导的产热、脂肪酸氧化和产热，从而总结了体内冷诱导的FGF21分泌与冷诱导的产热之间的关系。米色脂肪细胞在人类中是产热的。FGF21是一种米色脂肪因子，能够促进褐色脂肪样产热程序。这项研究提供了人类颈部脂肪诱导功能性热源米色脂肪生成的第一个证据。FGF21有望作为一种冷诱导的米色脂肪因子，通过白色脂肪组织的褐化具有代谢益处。
Recent studies suggest human neck brown adipose tissue (BAT) to consist of ‘brown adipocyte (BA)-like’ or beige adipocytes. However, little is known about their thermogenic function. Within the beige adipocyte transcriptome, fibroblast growth factor-21 (FGF21) is a gene whose protein product acts as an adipokine, regulating cold-induced thermogenesis in animals. Here, we explored (i) the adipogenic potential, thermogenic function and FGF21 secretory capacity of beige adipocytes derived from human neck fat and (ii) the role of FGF21 in modulating adipose bioenergetics. Progenitors isolated from human cervical fat were differentiated into adipocytes with either a BA-like or white adipocyte (WA) phenotype. FGF21 secretion was measured by enzyme-linked immuosorbent assay. Real-time PCR/western blotting was used to determine cellular mRNA/protein levels. Extracellular flux bioanalyzer was used to quantify adipocyte oxygen consumption and fatty acid oxidation. Adipocyte heat production was measured by infrared thermography. Under hormonal manipulation, primary human neck pre-adipocytes differentiated into adipocytes with either BA-like or WA phenotypes, on gene/protein and functional levels. BA-like cells expressed beige but not classic BA markers. During BA differentiation, FGF21 gene expression and secretion were increased, and were augmented following norepinephrine exposure (a cold mimic in vitro). Differentiated WA expressed β-klotho, a critical co-factor mediating FGF21 action. Treatment of WA with FGF21-induced UCP1 expression and increased oxygen consumption, respiratory uncoupling, norepinephrine-mediated thermogenesis, fatty acid oxidation and heat production, thus recapitulating the association between cold-induced FGF21 secretion and cold-induced thermogenesis in vivo. Beige adipocytes are thermogenic in humans. FGF21 is a beige adipokine capable of promoting a brown fat-like thermogenic program in WAs. This study provides first evidence of inducible functional thermogenic beige adipogenesis in human neck fat. FGF21 holds promise as a cold-induced beige adipokine with metabolic benefits of therapeutic relevance through browning of white adipose tissue.
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DOI：
10.1073/pnas.0701600104
发表时间：
2007-05-01
影响因子：
11.1
作者：
Ogawa, Yasushi;Kurosu, Hiroshi;Kuro-o, Makoto
通讯作者：
Kuro-o, Makoto
影响因子：
7.7
作者：
Saito M;Okamatsu-Ogura Y;Matsushita M;Watanabe K;Yoneshiro T;Nio-Kobayashi J;Iwanaga T;Miyagawa M;Kameya T;Nakada K;Kawai Y;Tsujisaki M
通讯作者：
Tsujisaki M
影响因子：
5.7
作者：
Chartoumpekis, Dionysios V.;Habeos, Ioannis G.;Papavassiliou, Athanasios G.
通讯作者：
Papavassiliou, Athanasios G.
影响因子：
4.8
作者：
Lee, Paul;Swarbrick, Michael M.;Ho, Ken K. Y.
通讯作者：
Ho, Ken K. Y.
影响因子：
158.5
作者：
Virtanen, Kirsi A.;Lidell, Martin E.;Nuutila, Pirjo
通讯作者：
Nuutila, Pirjo