High-Fat Diet-Induced Obesity Alters Dendritic Cell Homeostasis by Enhancing Mitochondrial Fatty Acid Oxidation.

Autor:	Chen IC; Department of Medicine, Weill Cornell Medicine, New York, NY.; Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan.; Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.; Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan., Awasthi D; Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, NY.; Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY., Hsu CL; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan., Song M; Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, NY.; Department of Integrative Biotechnology and Biopharmaceutical Convergence, Sungkyunkwan University, Suwon, Gyeonggi-do, Korea; and., Chae CS; Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, NY.; Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY., Dannenberg AJ; Department of Medicine, Weill Cornell Medicine, New York, NY., Cubillos-Ruiz JR; Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, NY; jur2016@med.cornell.edu.; Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY.; Weill Cornell Graduate School of Medical Sciences, Cornell University. New York, NY.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2022 Jul 01; Vol. 209 (1), pp. 69-76. Date of Electronic Publication: 2022 Jun 13.
DOI:	10.4049/jimmunol.2100567
Abstrakt:	Obesity is associated with increased cancer risk and weak responses to vaccination and sepsis treatment. Although dendritic cells (DCs) are fundamental for the initiation and maintenance of competent immune responses against pathogens and tumors, how obesity alters the normal physiology of these myeloid cells remains largely unexplored. In this study, we report that obesity caused by prolonged high-fat diet feeding disrupts the metabolic and functional status of mouse splenic DCs (SpDCs). High-fat diet-induced obesity drastically altered the global transcriptional profile of SpDCs, causing severe changes in the expression of gene programs implicated in lipid metabolism and mitochondrial function. SpDCs isolated from obese mice demonstrated enhanced mitochondrial respiration provoked by increased fatty acid oxidation (FAO), which drove the intracellular accumulation of reactive oxygen species that impaired Ag presentation to T cells. Accordingly, treatment with the FAO inhibitor etomoxir, or antioxidants such as vitamin E or N -acetyl-l-cysteine, restored the Ag-presenting capacity of SpDCs isolated from obese mice. Our findings reveal a major detrimental effect of obesity in DC physiology and suggest that controlling mitochondrial FAO or reactive oxygen species overproduction may help improve DC function in obese individuals. (Copyright © 2022 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu