![]() These cellular metabolites are either fully oxidized in mitochondria (for example, via the TCA cycle, fatty acid oxidation and oxidative phosphorylation by the electron transport chain ), used for the production of cellular building blocks (for example, in amino acid, nucleotide or fatty acid synthesis ) or released from the cells to prevent toxicity (for example, lactate or excess cholesterol). In short, tissue fuels (such as glucose, lipids or amino acids) are converted into metabolites (such as pyruvate, tricarboxylic acid cycle intermediates, fatty acids or free cholesterol) by several metabolic reactions (such as glycolysis, lipolysis or glutaminolysis). Moreover, disease can change the tissue microenvironment and consequently affect macrophage metabolism and function in turn, macrophage metabolism may be key for disease resolution or progression.Ĭellular metabolism is a complex network that is essential for cellular fitness and consists of catabolic processes (degradation of nutrients, predominantly for metabolite or energy generation in mitochondria) and anabolic processes (use of metabolites for synthesis of cellular structures). These observations suggest that tissue-resident macrophage identity requires a certain metabolic state that may depend on the availability of metabolites or nutrients and, importantly, facilitates their tissue-specific function. In vitro studies in the context of pro- or anti-inflammatory activation highlight the metabolic plasticity of macrophages, which can completely rewire aspects of their cellular metabolism-bioenergetics, nutrient usage, generation of metabolites/cellular building blocks, etc.-depending on the task at hand. Interestingly, several of these signature macrophage transcription factors regulate fundamental metabolic features. ![]() These mostly tissue-specific transcriptional programs are vital for the functions, maintenance and phenotypes of tissue macrophages. Indeed, after loss of resident macrophages, incoming monocytes are reprogrammed by environmental macrophage niches to adopt the transcriptional programs that define the resident population. Seminal studies have shown that the identity of macrophage populations is imprinted by the residing tissue, which is evidenced by the expression of tissue-associated signature transcription factors. However, the compositions and requirements of different microenvironments and niches differ notably, demanding distinct functions from their resident macrophages. They colonize tissues to form self-maintaining populations, can be replenished by circulating monocytes following insults or are constantly differentiating from infiltrating monocytes. Indeed, macrophages are present in virtually every organ of the body. Macrophages are tissue-resident immune cells that act as important immune sentinels and concomitantly execute vital homeostatic tasks to ensure tissue integrity and functionality. ![]() Here, we outline current knowledge on the metabolic requirements and adaptations of macrophages located in tissues during homeostasis and selected diseases. This context specificity creates diverging metabolic challenges for tissue macrophage populations to fulfill their homeostatic roles in their particular microenvironment and conditions their response in pathological conditions. However, different organs contain diverse macrophage populations that specialize in distinct and often tissue-specific functions. Macrophage metabolism has largely been studied in vitro. Macrophages are embryo- or adult bone marrow-derived leukocytes that are key for healthy tissue homeostasis but can also contribute to pathologies such as metabolic syndrome, atherosclerosis, fibrosis or cancer. ![]() The emerging field of immunometabolism highlights the importance of cellular metabolism for the maintenance and activities of immune cells. Cellular metabolism orchestrates the intricate use of tissue fuels for catabolism and anabolism to generate cellular energy and structural components. ![]()
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