TY - JOUR
T1 - Prkaa1 Metabolically Regulates Monocyte/Macrophage Recruitment and Viability in Diet-Induced Murine Metabolic Disorders
AU - Yang, Qiuhua
AU - Ma, Qian
AU - Xu, Jiean
AU - Liu, Zhiping
AU - Zou, Jianqiu
AU - Shen, Jian
AU - Zhou, Yaqi
AU - Da, Qingen
AU - Mao, Xiaoxiao
AU - Lu, Sarah
AU - Fulton, David J
AU - Weintraub, Neal L
AU - Bagi, Zsolt
AU - Hong, Mei
AU - Huo, Yuqing
N1 - Funding Information:
This work was supported by the National Science Foundation of China (Grant 81870324); Shenzhen Science and Technology Innovation Committee (Grants JCYJ20190808155605447, JCYJ20170810163238384, JCYJ20190808155801648, and JCYJ20170412150405310); Guangdong Natural Science Foundation (Grants 2020A1515010010 and 2014A030312004); Shenzhen-Hong Kong Institute of Brain Science–Shenzhen Fundamental Research Institutions (2019SHIBS0004); China Postdoctoral Science Foundation (8206300346); American Heart Association (Grants 19POST34430119 and 19TPA34910043); National Institutes of Health (Grants R01HL134934, R01EY030500, R01HL142097, and R01HL138410); and VA Merit Review (Grant BX002035).
Funding Information:
Funding. This work was supported by the National Science Foundation of China (Grant 81870324); Shenzhen Science and Technology Innovation Committee (Grants JCYJ20190808155605447, JCYJ20170810163238384, JCYJ20190808155801648, and JCYJ20170412150405310); Guangdong Natural Science Foundation (Grants 2020A1515010010 and 2014A030312004); Shenzhen-Hong Kong Institute of Brain Science?Shenzhen Fundamental Research Institutions (2019SHIBS0004); China Postdoctoral Science Foundation (8206300346); American Heart Association (Grants 19POST34430119 and 19TPA34910043); National Institutes of Health (Grants R01HL134934, R01EY030500, R01HL142097, and R01HL138410); and VA Merit Review (Grant BX002035).
Publisher Copyright:
© Copyright © 2021 Yang, Ma, Xu, Liu, Zou, Shen, Zhou, Da, Mao, Lu, Fulton, Weintraub, Bagi, Hong and Huo.
PY - 2020
Y1 - 2020
N2 - Myeloid cells, including monocytes/macrophages, primarily rely on glucose and lipid metabolism to provide the energy and metabolites needed for their functions and survival. AMP-activated protein kinase (AMPK, its gene is PRKA for human, Prka for rodent) is a key metabolic sensor that regulates many metabolic pathways. We studied recruitment and viability of Prkaa1-deficient myeloid cells in mice and the phenotype of these mice in the context of cardio-metabolic diseases. We found that the deficiency of Prkaa1 in myeloid cells downregulated genes for glucose and lipid metabolism, compromised glucose and lipid metabolism of macrophages, and suppressed their recruitment to adipose, liver and arterial vessel walls. The viability of macrophages in the above tissues/organs was also decreased. These cellular alterations resulted in decreases in body weight, insulin resistance, and lipid accumulation in liver of mice fed with a high fat diet, and reduced the size of atherosclerotic lesions of mice fed with a Western diet. Our results indicate that AMPKα1/PRKAA1-regulated metabolism supports monocyte recruitment and macrophage viability, contributing to the development of diet-induced metabolic disorders including diabetes and atherosclerosis.
AB - Myeloid cells, including monocytes/macrophages, primarily rely on glucose and lipid metabolism to provide the energy and metabolites needed for their functions and survival. AMP-activated protein kinase (AMPK, its gene is PRKA for human, Prka for rodent) is a key metabolic sensor that regulates many metabolic pathways. We studied recruitment and viability of Prkaa1-deficient myeloid cells in mice and the phenotype of these mice in the context of cardio-metabolic diseases. We found that the deficiency of Prkaa1 in myeloid cells downregulated genes for glucose and lipid metabolism, compromised glucose and lipid metabolism of macrophages, and suppressed their recruitment to adipose, liver and arterial vessel walls. The viability of macrophages in the above tissues/organs was also decreased. These cellular alterations resulted in decreases in body weight, insulin resistance, and lipid accumulation in liver of mice fed with a high fat diet, and reduced the size of atherosclerotic lesions of mice fed with a Western diet. Our results indicate that AMPKα1/PRKAA1-regulated metabolism supports monocyte recruitment and macrophage viability, contributing to the development of diet-induced metabolic disorders including diabetes and atherosclerosis.
KW - AMPKα1/PRKAA1
KW - glycolysis
KW - macrophage viability
KW - metabolic disorders
KW - monocyte recruitment
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U2 - 10.3389/fcell.2020.611354
DO - 10.3389/fcell.2020.611354
M3 - Article
C2 - 33511118
AN - SCOPUS:85099961319
SN - 2296-634X
VL - 8
SP - 611354
JO - Frontiers in Cell and Developmental Biology
JF - Frontiers in Cell and Developmental Biology
M1 - 611354
ER -