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Fueling defense: PPARα enhances macrophage inflammatory responses

Cellular & Molecular Immunology volume 22, pages 461–462 (2025)Cite this article

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The Original Article was published on 05 February 2025

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While angiotensin-converting enzyme (ACE) is traditionally known for its ability to regulate blood pressure and fluid balance through the renin‒angiotensin system, ACE also plays a pivotal role in immune activation [1]. Macrophages in which ACE is overexpressed display enhanced inflammatory responses, as evidenced by increased antitumor and antibacterial activity [2]. This increase in inflammation coincides with increased lipid metabolism and ATP production [3, 4]. The mechanisms by which ACE enhances cellular metabolism and inflammation remain unknown. In this issue of Cellular and Molecular Immunology, Saito et al. [5] provide compelling evidence that peroxisome proliferator-activated receptor α (PPARα) is central to the observed enhanced immune capabilities of macrophages overexpressing ACE.

The inflammatory potential of macrophages is intrinsically tied to cellular metabolic processes, especially lipid metabolism. Macrophages rely on their metabolic adaptability to meet the demands of the diverse microenvironments in which they reside. Macrophage behavior and function are particularly regulated by lipid metabolism. Lipid metabolic pathways in alveolar macrophages and Kupffer cells accelerate their potential in maintaining tissue homeostasis by clearing lipids and apoptotic cells [6, 7]. Increased mitochondrial and lipid metabolism is usually associated with anti-inflammatory macrophage phenotypes [8,9,10]; however, recent work in obese white adipose tissue has shown that inflammatory macrophages can also rely on mitochondrial metabolism to process the lipid overload caused by overnutrition [11].

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  1. Department of Medical Biochemistry, Amsterdam institute for Immunology and Infectious Diseases, Immunology, Amsterdam Cardiovascular Sciences, Atherosclerosis, Amsterdam UMC, location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands

    Marten A. Hoeksema

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Hoeksema, M.A. Fueling defense: PPARα enhances macrophage inflammatory responses. Cell Mol Immunol 22, 461–462 (2025). https://doi.org/10.1038/s41423-025-01265-y

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