Exposure to cold alters glucose and lipid metabolism of white and brown adipose tissue via activation of β-adrenergic receptor (ADRB). Fibroblast growth factor 21 (FGF21) has been shown to be locally released from adipose tissue upon activation of ADRBs and FGF21 increases glucose uptake in adipocytes. Therefore, FGF21 may play an autocrine role in inducing glucose uptake after β-adrenergic stimulation. To determine the putative autocrine role of FGF21, we stimulated three different types of adipocytes in vitro with Isoprenaline (Iso), an ADRB agonist, in the presence or absence of the FGF receptor (FGFR) inhibitor PD 173074. The three cell lines represent white (3T3-L1), beige (ME3) and brown (WT-1) adipocyte phenotypes, respectively. All three cells systems expressed β-klotho (KLB) and FGFR1 after differentiation and treatment with recombinant FGF21 increased glucose uptake in 3T3-L1 and WT-1 adipocytes, while no significant effect was observed in ME3. Oppositely, all three cell lines responded to Iso treatment and an increase in glucose uptake and lipolysis were observed. Interestingly, in response to the Iso treatment only the WT-1 adipocytes showed an increase in FGF21 in the medium. This was consistent with the observation that PD 173074 decreased Iso-induced glucose uptake in the WT-1 adipocytes. This suggests that FGF21 plays an autocrine role and increases glucose uptake after β-adrenergic stimulation of cultured brown WT-1 adipocytes.

中文翻译：

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FGF21在培养的脂肪细胞中的自分泌作用。

暴露于寒冷中会通过激活β-肾上腺素能受体（ADRB）改变白色和棕色脂肪组织的葡萄糖和脂质代谢。已显示成纤维细胞生长因子21（FGF21）在ADRB激活后会从脂肪组织中局部释放，而FGF21可增加脂肪细胞中的葡萄糖摄取。因此，FGF21在β-肾上腺素刺激后可能在诱导葡萄糖摄取中起自分泌作用。为了确定FGF21的假定自分泌作用，我们在存在或不存在FGF受体（FGFR）抑制剂PD 173074的情况下，用异丙肾上腺素（Iso）（一种ADRB激动剂）在体外刺激了三种不同类型的脂肪细胞。这三种细胞系代表白色（3T3-L1），米色（ME3）和棕色（WT-1）脂肪细胞表型。分化后所有三个细胞系统均表达β-klotho（KLB）和FGFR1，重组FGF21处理可增加3T3-L1和WT-1脂肪细胞的葡萄糖摄取，而在ME3中未观察到显着影响。相反，所有三个细胞系均对Iso处理有反应，并且观察到葡萄糖摄取和脂解作用的增加。有趣的是，响应于Iso处理，仅WT-1脂肪细胞在培养基中显示出FGF21的增加。这与PD 173074降低WT-1脂肪细胞中Iso诱导的葡萄糖摄取的观察结果一致。这表明在培养的棕色WT-1脂肪细胞经过β-肾上腺素刺激后，FGF21发挥自分泌作用并增加葡萄糖摄取。所有三个细胞系均对Iso处理有反应，并观察到葡萄糖摄取和脂解作用的增加。有趣的是，响应于Iso处理，仅WT-1脂肪细胞在培养基中显示出FGF21的增加。这与PD 173074降低WT-1脂肪细胞中Iso诱导的葡萄糖摄取的观察结果一致。这表明在培养的棕色WT-1脂肪细胞经过β-肾上腺素刺激后，FGF21发挥自分泌作用并增加葡萄糖摄取。所有三个细胞系均对Iso处理有反应，并观察到葡萄糖摄取和脂解作用的增加。有趣的是，响应于Iso处理，仅WT-1脂肪细胞在培养基中显示出FGF21的增加。这与PD 173074降低WT-1脂肪细胞中Iso诱导的葡萄糖摄取的观察结果一致。这表明在培养的棕色WT-1脂肪细胞经过β-肾上腺素刺激后，FGF21发挥自分泌作用并增加葡萄糖摄取。