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Prkaa1 Metabolically Regulates Monocyte/Macrophage Recruitment and Viability in Diet-Induced Murine Metabolic Disorders.


ABSTRACT: 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 AMPK?1/PRKAA1-regulated metabolism supports monocyte recruitment and macrophage viability, contributing to the development of diet-induced metabolic disorders including diabetes and atherosclerosis.

SUBMITTER: Yang Q 

PROVIDER: S-EPMC7835533 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Prkaa1 Metabolically Regulates Monocyte/Macrophage Recruitment and Viability in Diet-Induced Murine Metabolic Disorders.

Yang Qiuhua Q   Ma Qian Q   Xu Jiean J   Liu Zhiping Z   Zou Jianqiu J   Shen Jian J   Zhou Yaqi Y   Da Qingen Q   Mao Xiaoxiao X   Lu Sarah S   Fulton David J DJ   Weintraub Neal L NL   Bagi Zsolt Z   Hong Mei M   Huo Yuqing Y  

Frontiers in cell and developmental biology 20210112


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 <i>PRKA</i> for human, <i>Prka</i> for rodent) is a key metabolic sensor that regulates many metabolic pathways. We studied recruitment and viability of <i>Prkaa1</i>-deficient myeloid cells in mice and the phenotype of these mice in the context of cardio-metabolic diseases. We  ...[more]

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