Adipose-specific C-C motif chemokine ligand (CCL) 19 overexpression drives the mice to both insulin resistance and weight gain.

Adipose-specific C-C motif chemokine ligand (CCL) 19 overexpression drives the mice to both insulin resistance and weight gain.
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脂肪特异性C-C基序趋化因子配体(CCL)19过表达将小鼠驱动到胰岛素抵抗和体重增加。

DOI:
10.1136/bmjdrc-2020-001871
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发表时间:
2021-05
影响因子:
4.1
通讯作者:
Nishimura F
Nishimura F
中科院分区:
医学3区
文献类型:
--
作者:
Hayashi M;Iwashita M;Nishimura Y;Shinjo T;Sano T;Yamashita A;Fukuda T;Sanui T;Asano T;Nishimura F

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增大的脂肪组织的特征在于活化的免疫细胞的浸润和募集这些细胞的趋化因子(包括C-C基序配体19(CCL 19))的表达增加,尽管脂肪CCL 19的作用仍不确定。制备脂肪细胞特异性CCL 19基因敲入(KI)小鼠,并给小鼠喂食正常饮食或40%或60%脂肪饮食(FD)以研究CCL 19对炎症诱导和脂质代谢的影响。与野生型(WT)小鼠相比,Ccl 19 KI小鼠脂肪组织中的炎症体征增加,皮下白色和棕色脂肪组织增大。Ccl 19 KI小鼠脂肪组织的特征是细胞外信号调节激酶1/2增加和AMP活化蛋白激酶α磷酸化减少。与WT小鼠相比,Ccl 19 KI小鼠棕色脂肪组织中过氧化物酶体增殖物激活受体γ共激活因子1α和解偶联蛋白1的蛋白表达显著降低。在喂食40%FD的小鼠中观察到基因型之间最显著的变化。40%FD增强了CCL 19过表达的作用,这些小鼠可能是研究超重亚洲人代谢紊乱的合适模型。
Enlarged adipose tissue is characterized by infiltration of activated immune cells and increased expression of chemokines recruiting these cells including C-C motif ligand 19 (CCL19), although the role of adipose CCL19 is still inconclusive. Adipocyte-specific Ccl19 knock-in (KI) mice were generated, and the mice were fed either a normal diet or 40% or 60% fat diet (FD) to investigate the effects of CCL19 on the induction of inflammation and lipid metabolism. Ccl19KI mice exhibited increased inflammatory signs in adipose tissue and enlarged subcutaneous white and brown adipose tissue than those of wild-type (WT) mice. The adipose tissue of Ccl19KI mice was characterized by increased extracellular signal-regulated kinase 1/2 and decreased AMP-activated protein kinase α phosphorylation. The protein expression of peroxisome proliferator-activated receptor γ coactivator 1α and uncoupling protein 1 was significantly reduced in brown adipose tissue of Ccl19KI mice compared with that in WT mice. The most remarkable changes between genotypes were observed in mice fed a 40% FD. A 40% FD enhanced the effects of CCL19 overexpression, and these mice could be a suitable model to study metabolic disorders in overweight Asians.
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