Fate of adipocyte progenitors during adipogenesis in mice fed a high-fat diet.
Fate of adipocyte progenitors during adipogenesis in mice fed a high-fat diet.
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脂肪生成过程中脂肪细胞祖细胞的命运在喂养高脂饮食的小鼠中。
DOI：
10.1016/j.molmet.2021.101328
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发表时间：
2021-12
影响因子：
8.1
通讯作者：
Tobe K
中科院分区：
文献类型：
--
作者：
Bilal M;Nawaz A;Kado T;Aslam MR;Igarashi Y;Nishimura A;Watanabe Y;Kuwano T;Liu J;Miwa H;Era T;Ikuta K;Imura J;Yagi K;Nakagawa T;Fujisaka S;Tobe K
肥胖期间通过募集新生成的脂肪细胞（增生）而使脂肪组织扩张在代谢上是健康的，而通过使预先存在的脂肪细胞增大（肥大）而导致代谢并发症。来自遗传命运作图研究的累积证据表明，在接受高脂饮食（HFD）的动物模型中，仅性腺白色脂肪组织（gWAT）中的脂肪细胞祖细胞（AP）具有增殖潜力。然而，雄性小鼠腹股沟WAT（iWAT）中AP的增殖潜力和分化能力仍然存在争议。本研究的目的是研究AP在HFD喂养的雄性小鼠的iWAT中的增殖和成脂潜力。我们产生了PDGFRα-GFP-Cre-ERT 2/tdTomato（KI/td）小鼠，并在喂食HFD 8周的雄性小鼠中追踪PDGFRα阳性AP。我们进行了全面的表型分析，包括组织学，免疫组织化学，流式细胞术，基因表达分析，KI/td小鼠喂食HFD。与其他人的发现相反，我们发现雄性小鼠iWAT中新生成的tdTomato+脂肪细胞数量增加，小于gWAT中观察到的数量。我们发现，在雄性小鼠中，iWAT具有比gWAT更多的增殖性tdTomato+ AP。我们还发现，tdTomato+ AP显示出比tdTomato− AP更高的Dpp 4和Pi 16表达，并且这些基因在喂食HFD 8周的小鼠的iWAT中的表达显著高于gWAT。总的来说，我们的结果表明，HFD喂养诱导雄性小鼠iWAT中tdTomato+ AP的增殖。在雄性小鼠中，与gWAT相比，iWAT响应8周的HFD喂养，通过招募新生成的脂肪细胞而发生增生，这是由于大量具有高增殖和分化潜力的AP。高脂饮食（HFD）增加雄性小鼠iWAT中的增殖AP。HFD促进雄性小鼠iWAT中较小脂肪细胞的募集。iWAT通过在雄性小鼠中招募新生成的脂肪细胞（增生）来扩增。gWAT通过雄性小鼠中预先存在的脂肪细胞的增大（肥大）而扩展。
Expansion of adipose tissue during obesity through the recruitment of newly generated adipocytes (hyperplasia) is metabolically healthy, whereas that through the enlargement of pre-existing adipocytes (hypertrophy) leads to metabolic complications. Accumulating evidence from genetic fate mapping studies suggests that in animal models receiving a high-fat diet (HFD), only adipocyte progenitors (APs) in gonadal white adipose tissue (gWAT) have proliferative potential. However, the proliferative potential and differentiating capacity of APs in the inguinal WAT (iWAT) of male mice remains controversial. The objective of this study was to investigate the proliferative and adipogenic potential of APs in the iWAT of HFD-fed male mice. We generated PDGFRα-GFP-Cre-ERT2/tdTomato (KI/td) mice and traced PDGFRα-positive APs in male mice fed HFD for 8 weeks. We performed a comprehensive phenotypic analysis, including the histology, immunohistochemistry, flow cytometry, and gene expression analysis, of KI/td mice fed HFD. Contrary to the findings of others, we found an increased number of newly generated tdTomato+ adipocytes in the iWAT of male mice, which was smaller than that observed in the gWAT. We found that in male mice, the iWAT has more proliferating tdTomato+ APs than the gWAT. We also found that tdTomato+ APs showed a higher expression of Dpp4 and Pi16 than tdTomato− APs, and the expression of these genes was significantly higher in the iWAT than in the gWAT of mice fed HFD for 8 weeks. Collectively, our results reveal that HFD feeding induces the proliferation of tdTomato+ APs in the iWAT of male mice. In male mice, compared with gWAT, iWAT undergoes hyperplasia in response to 8 weeks of HFD feeding through the recruitment of newly generated adipocytes due to an abundance of APs with a high potential for proliferation and differentiation. High-fat diet (HFD) increases proliferative APs in iWAT of male mice. HFD promotes the recruitment of smaller adipocytes in the iWAT of male mice. iWAT expands by recruiting newly-generated adipocytes (hyperplasia) in male mice. gWAT expands by enlargement of pre-existing adipocytes (hypertrophy) in male mice.
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影响因子：
29
作者：
Berry R;Jeffery E;Rodeheffer MS
通讯作者：
Rodeheffer MS
影响因子：
4.6
作者：
Horikawa S;Ishii Y;Hamashima T;Yamamoto S;Mori H;Fujimori T;Shen J;Inoue R;Nishizono H;Itoh H;Majima M;Abraham D;Miyawaki T;Sasahara M
通讯作者：
Sasahara M
影响因子：
2.5
作者：
Ding, Guo;Tanaka, Yosuke;Hayashi, Misato;Nishikawa, Shin-Ichi;Kataoka, Hiroshi
通讯作者：
Kataoka, Hiroshi
影响因子：
3.7
作者：
Kuwano T;Izumi H;Aslam MR;Igarashi Y;Bilal M;Nishimura A;Watanabe Y;Nawaz A;Kado T;Ikuta K;Yamamoto S;Sasahara M;Fujisaka S;Yagi K;Mori H;Tobe K
通讯作者：
Tobe K
影响因子：
29
作者：
Jeffery E;Wing A;Holtrup B;Sebo Z;Kaplan JL;Saavedra-Peña R;Church CD;Colman L;Berry R;Rodeheffer MS
通讯作者：
Rodeheffer MS