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 AMPKα1/PRKAA1-regulated metabolism supports monocyte recruitment and macrophage viability, contributing to the development of diet-induced metabolic disorders including diabetes and atherosclerosis.
Highlights
Metabolic syndrome, including obesity and diabetes as well as their vascular complications such as atherosclerosis, are chronic inflammatory diseases (Ross, 1999; Libby, 2002; Weisberg et al, 2003; Xu et al, 2003; Lumeng and Saltiel, 2011)
The results showed that the mRNA levels of Prkaa1 and Prkaa2 were much higher in leukocytes from adipose tissues of mice fed highfat diet (HFD) for 8 weeks than mice fed chow diet (CD) (Figure 1B)
Since macrophages are the predominate leukocytes infiltrating in adipose, we examined the expression of Prkaa1 and some of the above metabolic molecules in F4/80-positive cells by immunostaining adipose sections with the relevant antibodies
Summary
Metabolic syndrome, including obesity and diabetes as well as their vascular complications such as atherosclerosis, are chronic inflammatory diseases (Ross, 1999; Libby, 2002; Weisberg et al, 2003; Xu et al, 2003; Lumeng and Saltiel, 2011). These diseases are initiated by recruitment of circulating leukocytes, including monocytes, T cells, neutrophils, and NK cells, to the metabolic organs/tissues. The infiltrated leukocytes survive in the affected organs/tissues, modulate their activation status and subsequently conquer the progression of these metabolic disorders and their complications. Less is known about the impact of metabolic alterations on leukocyte recruitment and survival in diet-induced metabolic syndrome
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