Ghrelin effects on mitochondrial fitness modulates macrophage function

Author(s):Show less -

da Silva, Felipe Correa ^[1] ; Aguiar, Cristhiane ^[1] ; Pereira, Jessica A. S. ^{[2, 1]} ; Monteiro, Lauar de Brito ^[1] ; Davanzo, Gustavo Gastao ^[1] ; Codo, Ana Campos ^[1] ; de Freitas, Leonardo Pimentel ^[1] ; Berti, Aline Siqueira ^[3] ; Ferrucci, Danilo Lopes ^[3] ; Castelucci, Bianca Gazieri ^[4] ; Consonni, Silvio Roberto ^[4] ; Carvalho, Hernandes F. ^[3] ; Moraes-Vieira, Pedro M. M. ^{[2, 1]}

Affiliation

^[1] Univ Estadual Campinas, Lab Immunometab, Dept Genet Evolut Microbiol & Immunol, Campinas, SP - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo - Brazil

^[3] Univ Estadual Campinas, Dept Struct & Funct Biol, Lab Extracellular Matrix, Campinas, SP - Brazil

^[4] Univ Estadual Campinas, Dept Biochem & Tissue Biol, Lab Cytochem & Immunocytochem, Campinas, SP - Brazil

• Document type: Journal article
• Source: Free Radical Biology and Medicine; v. 145, p. 61-66, DEC 2019.
• Web of Science Citations: 0

Abstract

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-alpha and IL-beta 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-alpha and enhanced IL-12 levels. Moreover, ghrelin effects on IL-12, and not on TNF-alpha, are dependent on mitochondria elongation, since ghrelin did not enhance IL-12 secretion in metabolic activated mitofusin-2 deficient macrophages. Thus, ghrelin affects macrophage mitochondrial metabolism and the subsequent macrophage function. (AU)

• FAPESP's process: 17/23679-0 - Study of the function of LXRs receptors in the modulation of t CD4 + lymphocytes in vitro and in vivo
• Grantee: Leonardo Pimentel de Freitas
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 16/18031-8 - HIF-1 alpha in metabolic and functional control of adipose tissue resident macrophages in diabetes induced by obesity
• Grantee: Gustavo Gastão Davanzo
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/12848-5 - Studying NKT cell metabolism in obesity and metabolic syndrome
• Grantee: Cristhiane Favero de Aguiar
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/22505-0 - Effect of 12-oleic acid ester of hydroxy fatty acid (12-OAHSA) on inflammatory and metabolic pathways of macrophage activation
• Grantee: Ana Campos Codo
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 15/15626-8 - Macrophages and T lymphocytes immunometabolism in metabolic and inflammatory diseases
• Grantee: Pedro Manoel Mendes de Moraes Vieira
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 17/00079-7 - Effects of LXRs receptor activation on systemic metabolic parameters and on the metabolic modulation of resident tissue macrophages of adipose tissue
• Grantee: Jéssica Aparecida da Silva Pereira
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/06225-5 - Influence of synthetic ([Nle 4, D-Phe7] -±-MSH on microglia metabolism: possible implications on obesity development
• Grantee: Felipe Corrêa da Silva
• Support Opportunities: Scholarships in Brazil - Master