TY - JOUR
T1 - Adipose-specific C-C motif chemokine ligand (CCL) 19 overexpression drives the mice to both insulin resistance and weight gain
AU - Hayashi, Masato
AU - Iwashita, Misaki
AU - Nishimura, Yuki
AU - Shinjo, Takanori
AU - Sano, Tomomi
AU - Yamashita, Akiko
AU - Fukuda, Takao
AU - Sanui, Terukazu
AU - Asano, Tomoichiro
AU - Nishimura, Fusanori
N1 - Funding Information:
Funding This work was supported by JSPS KAKENHI Grant Numbers JP16H05555 and JP19K10152.
Publisher Copyright:
© 2021 Author(s). Published by BMJ.
PY - 2021/5/24
Y1 - 2021/5/24
N2 - 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 α phosphorylation. The protein expression of peroxisome proliferator-activated receptor γcoactivator 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. 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.
AB - 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 α phosphorylation. The protein expression of peroxisome proliferator-activated receptor γcoactivator 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. 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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U2 - 10.1136/bmjdrc-2020-001871
DO - 10.1136/bmjdrc-2020-001871
M3 - Article
C2 - 34031140
AN - SCOPUS:85106857686
SN - 2052-4897
VL - 9
JO - BMJ Open Diabetes Research and Care
JF - BMJ Open Diabetes Research and Care
IS - 1
M1 - e001871
ER -