Impaired adrenergic agonist-dependent beige adipocyte induction in obese mice
Impaired adrenergic agonist-dependent beige adipocyte induction in obese mice
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DOI：
10.1292/jvms.19-0070
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发表时间：
2019-04
期刊：
影响因子：
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通讯作者：
Woongchul Shin;Y. Okamatsu-Ogura;Shinya Matsuoka;Ayumi Tsubota;K. Kimura
中科院分区：
文献类型：
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作者：
Woongchul Shin;Y. Okamatsu-Ogura;Shinya Matsuoka;Ayumi Tsubota;K. Kimura
棕色脂肪细胞存在于棕色脂肪组织 (BAT) 中，可通过肾上腺素能刺激激活，具体取决于解偶联蛋白 1 (UCP1) 的活性。米色脂肪细胞从白色脂肪组织（WAT）中出现，以响应慢性肾上腺素能刺激。我们研究了小鼠中两种类型脂肪细胞对肾上腺素能刺激的反应与肥胖相关的变化。与正常饮食（ND：10%-kcal 脂肪）喂养相比，用高脂肪饮食（HFD：45%-kcal 脂肪）喂养小鼠 14 周，其体重和 WAT 重量显着升高。注射 β3-肾上腺素受体激动剂 CL316,243（CL；0.1 mg/kg，每天一次）一周，无论饮食如何，BAT 中 UCP1 的 mRNA 和蛋白表达水平都会升高。在WAT中，CL诱导ND小鼠中UCP1表达；然而，HFD 小鼠对 CL 治疗的反应减弱，表明肥胖小鼠中 CL 诱导的 WAT 褐变受到损害。流式细胞术分析显示，与 ND 小鼠相比，HFD 小鼠 WAT 中表达血小板衍生生长因子受体 (PDGFR) α 的米色脂肪细胞祖细胞显着减少。在 ND 小鼠中注射 CL 后，WAT 中 PDGF-B（一种 PDGFRα 配体）的表达增加，但在 HFD 小鼠中则没有。用 PDGFR 抑制剂治疗小鼠显着降低了 WAT 中 CL 依赖性 UCP1 蛋白的诱导。我们的研究表明，WAT 中 β3 肾上腺素能刺激依赖性米色脂肪细胞诱导受到小鼠肥胖的损害，这可能是由于肥胖依赖性表达 PDGFRα 的祖细胞数量减少和 PDGF-B 表达减少所致。
Brown adipocytes, which exist in brown adipose tissue (BAT), are activated by adrenergic stimulation, depending on the activity of uncoupling protein 1 (UCP1). Beige adipocytes emerge from white adipose tissue (WAT) in response to chronic adrenergic stimulation. We investigated obesity-related changes in responses of both types of adipocytes to adrenergic stimulation in mice. Feeding of mice with high-fat diets (HFD: 45%-kcal fat) for 14 weeks resulted in significantly higher body and WAT weight compared to feeding with normal diets (ND: 10%-kcal fat). Injection with β3-adrenergic receptor agonist CL316,243 (CL; 0.1 mg/kg, once a day) for one week elevated the mRNA and protein expression levels of UCP1 in BAT, irrespective of diet. In WAT, CL-induced UCP1 expression in ND mice; however, the responses to CL treatment were attenuated in HFD mice, indicating that CL-induced browning of WAT was impaired in obese mice. Flow cytometric analysis revealed a significant decrease in platelet-derived growth factor receptor (PDGFR) α-expressing beige adipocyte progenitors in WAT of HFD mice compared with those of ND mice. Expression of PDGF-B, a PDGFRα ligand, increased in WAT following CL-injection in ND mice, but not in HFD mice. Treatment of mice with a PDGFR inhibitor significantly decreased CL-dependent UCP1 protein induction in WAT. Our study demonstrates that β3-adrenergic stimulation-dependent beige adipocyte induction in WAT is impaired by obesity in mice, potentially due to obesity-dependent reduction in the number of PDGFRα-expressing progenitors and decreased PDGF-B expression.