Unraveling the metabolic demand of intestinal lamina propria macrophages and its role in Obesity and insulin resistance development

• Grant number: 17/00721-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2017
• End date: September 30, 2017
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Angela Castoldi
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Obesity can be described as a "new world syndrome", characterized by a low-grade inflammation. This systemic low-grade inflammation is mainly due to the systemic endotoxemia, which occurs in consequence of increased gut permeability, due to gut microbiota alterations and consequently increased leakage of endotoxins, such as lipopolysaccharide to the systemic circulation. Moreover, differences between immune cell metabolism in normal state and under activation were described. Importantly, CX3CR1+ cells from the own sheet represent a heterogeneous group of cells, which express high, low and intermediate levels of CX3CR1 together with F4/80 and CD11b. In the intestinal environment, the basal metabolism is already different from other tissues. The baseline O2 levels are uniquely low due to counter-current blood flow and the presence of large numbers of bacteria and mucus. Since residents CX3CR1+ lamina propria macrophages are surviving in this hypoxic microenvironment, they may have different energy requirements than others resident macrophages. Thus, identifying mechanisms that are modulating the metabolism of macrophages may facilitate the understanding of the inflammatory processes in the intestine during HFD feeding. Obesity is correlated with changes in gut microbiota, increased microbial metabolite secretion and absorption, increased intestinal permeability, and higher circulating LPS levels. Macrophage function is closely linked to intrinsic changes in cellular metabolism. Own sheet macrophages are at the interface between intestinal physiology and systemic biology, and I hypothesize that, under HFD, alterations in the metabolism of own sheet CX3CR1+ macrophages leads to a loss of intestinal barrier integrity and therefore the induction of systemic inflammation that is critical for the development of Obesity and insulin resistance. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CASTOLDI, ANGELA; SANIN, DAVID E.; BAKKER, NIKKI VAN TEIJLINGEN; AGUIAR, CRISTHIANE F.; MONTEIRO, LAUAR DE BRITO; RANA, NISHA; GRZES, KATARZYNA M.; KABAT, AGNIESZKA M.; CURTIS, JONATHAN; CAMERON, ALANNA M.; et al. Metabolic and functional remodeling of colonic macrophages in response to high-fat diet-induced obesity. ISCIENCE, v. 26, n. 10, p. 16-pg., 2023-10-20. (17/05264-7, 15/18121-4, 17/00721-0)