PPARdelta: A key modulator in the pathogenesis of diabetes mellitus and Mycobacterium tuberculosis co-morbidity.

Autor:	AlSaeed H; Immunology and Microbiology Department, Dasman Diabetes Institute, Al-Soor Street, Dasman, Kuwait, PO BOX 1180, Dasman 15462, State of Kuwait., Haider MJA; Department of Biological Sciences, Faculty of Science, Kuwait University, PO BOX 5969, Safat 13060, State of Kuwait., Alzaid F; Bioenergetics Department, Dasman Diabetes Institute, Kuwait City 15462, Kuwait.; Université Paris Cité, INSERM UMR-S1151, CNRS UMR-S8253, Institut Necker Enfants Malades, 75015 Paris, France., Al-Mulla F; Genetics and Bioinformatics Department, Dasman Diabetes Institute, Kuwait, Kuwait., Ahmad R; Immunology and Microbiology Department, Dasman Diabetes Institute, Al-Soor Street, Dasman, Kuwait, PO BOX 1180, Dasman 15462, State of Kuwait., Al-Rashed F; Immunology and Microbiology Department, Dasman Diabetes Institute, Al-Soor Street, Dasman, Kuwait, PO BOX 1180, Dasman 15462, State of Kuwait.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2024 May 22; Vol. 27 (7), pp. 110046. Date of Electronic Publication: 2024 May 22 (Print Publication: 2024).
DOI:	10.1016/j.isci.2024.110046
Abstrakt:	The interplay between lipid metabolism and immune response in macrophages plays a pivotal role in various infectious diseases, notably tuberculosis (TB). Herein, we illuminate the modulatory effect of heat-killed Mycobacterium tuberculosis (HKMT) on macrophage lipid metabolism and its implications on the inflammatory cascade. Our findings demonstrate that HKMT potently activates the lipid scavenger receptor, CD36, instigating lipid accumulation. While CD36 inhibition mitigated lipid increase, it unexpectedly exacerbated the inflammatory response. Intriguingly, this paradoxical effect was linked to an upregulation of PPARδ. Functional analyses employing PPARδ modulation revealed its central role in regulating both lipid dynamics and inflammation, suggesting it as a potential therapeutic target. Moreover, primary monocytic cells from diabetic individuals, a demographic at amplified risk of TB, exhibited heightened PPARδ expression and inflammation, further underscoring its pathological relevance. Targeting PPARδ in these cells effectively dampened the inflammatory response, offering a promising therapeutic avenue against TB. Competing Interests: The authors declare no competing interests. (© 2024 The Author(s).)
Databáze:	MEDLINE
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