Roles of circadian clocks in macrophage metabolism: implications in inflammation and metabolism of lipids, glucose, and amino acids

Apr 7, 2025American journal of physiology. Endocrinology and metabolism

How body clocks in immune cells affect inflammation and the use of fats, sugars, and proteins

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Abstract

Macrophage metabolism is influenced by circadian clock genes, which may play a role in chronic inflammatory disorders.

Macrophages regulate crucial metabolic processes, including glucose, lipid, and amino acid metabolism.
Perturbations in macrophage circadian cycles could contribute to the development of chronic inflammatory diseases.
Poor macrophage metabolism is linked to conditions such as atherosclerosis, diabetes, cardiovascular diseases, and liver dysfunction.
Understanding the relationship between clock genes and macrophage metabolism may inform treatment strategies for metabolic disorders.
Maintaining circadian homeostasis in macrophages is associated with improved function and potential therapeutic benefits.

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Macrophages are essential immune cells that play crucial roles in inflammation and tissue homeostasis and are important regulators of metabolic processes, such as the metabolism of glucose, lipids, and amino acids. The regulation of macrophage metabolism by circadian clock genes has been emphasized in many studies. Changes in metabolic profiles occurring after the perturbation of macrophage circadian cycles may underlie the etiology of several diseases. Specifically, chronic inflammatory disorders, such as atherosclerosis, diabetes, cardiovascular diseases, and liver dysfunction, are associated with poor macrophage metabolism. Developing treatment approaches that target metabolic and immunological ailments requires an understanding of the complex relationships among clock genes, disease etiology, and macrophage metabolism. This review explores the molecular mechanisms through which clock genes regulate lipid, amino acid, and glucose metabolism in macrophages and discusses their potential roles in the development and progression of metabolic disorders. The findings underscore the importance of maintaining circadian homeostasis in macrophage function as a promising avenue for therapeutic intervention in diseases involving metabolic dysregulation, given its key roles in inflammation and tissue homeostasis. Moreover, reviewing the therapeutic implications of circadian rhythm in macrophages can help minimize the side effects of treatment. Novel strategies may be beneficial in treating immune-related diseases caused by shifted and blunted circadian rhythms via light exposure, jet lag, seasonal changes, and shift work or disruption to the internal clock (such as stress or disease).

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Roles of circadian clocks in macrophage metabolism: implications in inflammation and metabolism of lipids, glucose, and amino acids

Abstract

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