4.4 Article

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

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出版社

BMJ PUBLISHING GROUP
DOI: 10.1136/bmjdrc-2020-001871

关键词

adipokines; inflammation; obesity

资金

  1. JSPS KAKENHI [JP16H05555, JP19K10152]

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The research shows that Ccl19KI mice exhibit more inflammatory signs and enlarged adipose tissue, and a 40% fat diet exacerbates the effects of CCL19 overexpression. These findings suggest that these mice could be a suitable model for studying metabolic disorders in overweight Asians.
Introduction 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. Research design and methods 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. Results 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 alpha phosphorylation. The protein expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha 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. Conclusion 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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