Ghrelin effects on mitochondrial fitness modulates macrophage function
Open accessAbstract
Over the past years, systemic derived cues that regulate cellular metabolism have been implicated in the regulation of immune responses. Ghrelin is an orexigenic hormone produced by enteroendocrine cells in the gastric mucosa with known immunoregulatory roles. The mechanism behind the function of ghrelin in immune cells, such as macrophages, is still poorly understood. Here, we explored the hypothesis that ghrelin leads to alterations in macrophage metabolism thus modulating macrophage function. We demonstrated that ghrelin exerts an immunomodulatory effect over LPS-activated peritoneal macrophages, as evidenced by inhibition of TNF-α and IL-1β secretion and increased IL-12 production. Concomitantly, ghrelin increased mitochondrial membrane potential and increased respiratory rate. In agreement, ghrelin prevented LPS-induced ultrastructural damage in the mitochondria. Ghrelin also blunted LPS-induced glycolysis. In LPS-activated macrophages, glucose deprivation did not affect ghrelin-induced IL-12 secretion, whereas the inhibition of pyruvate transport and mitochondria-derived ATP abolished ghrelin-induced IL-12 secretion, indicating a dependence on mitochondrial function. Ghrelin pre-treatment of metabolic activated macrophages inhibited the secretion of TNF-α and enhanced IL-12 levels. Moreover, ghrelin effects on IL-12, and not on TNF-α, are dependent on mitochondria elongation, since ghrelin did not enhance IL-12 secretion in metabolic activated mitofusin-2 deficient macr…
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Ghrelin acts as a mitochondrial mediator and enhances mitochondrial fitness upon inflammation in macrophages.
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- Authors
- Corrêa da Silva, F., Aguiar, C., Pereira, J. A. S., de Brito Monteiro, L., Davanzo, G. G., Codo, A. C., Pimentel de Freitas, L., Berti, A. S., Lopes Ferrucci, D., Castelucci, B. G., Consonni, S. R., Carvalho, H. F., & Moraes-Vieira, P. M. M.
- Affiliations
- Universidade Estadual de Campinas (UNICAMP) (BR)
- ORCID
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2019-12
- Volume
- 145
- Pages
- 61-66
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2973032212
- Cited by
- 22
- References
- 0
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 1 · 2019: 1
- FWCI
- 1.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Free Radical Biology and Medicine (acceptedVersion)
- PubMed (publishedVersion)
- Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- ghrelin, macrophage function, mitochondrial metabolism, immunomodulation, lipopolysaccharide stimulation, IL-12, TNF-α, mitochondrial membrane potential, glycolysis, pyruvate transport, mitofusin 2, mitochondrial ultrastructure, glucose deprivation
- MeSH terms
- Adenosine Triphosphate, Animals, Glycolysis, Inflammation, Lipopolysaccharides, Mitochondria, Nitric Oxide, Tumor Necrosis Factor-alpha, Signal Transduction, Gene Expression Regulation, Neoplastic, Macrophages, Peritoneal, Interleukin-12, Mice, Membrane Potential, Mitochondrial, Interleukin-1beta, Ghrelin
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