Metabolic and functional remodeling of colonic macrophages in response to high-fat diet-induced obesity

Author(s):Show less -

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. ; Caputa, George ; de Souza, Tiago Antonio ; Souto, Fabricio O. ; Buescher, Joerg M. ; Edwards-Hicks, Joy ; Pearce, Erika L. ; Pearce, Edward J. ; Camara, Niels Olsen Saraiva

• Document type: Journal article
• Source: ISCIENCE; v. 26, n. 10, p. 16-pg., 2023-10-20.

Abstract

Little is known about the effects of high-fat diet (HFD)-induced obesity on resident colonic lamina propria (LP) macrophages (LPMs) function and metabolism. Here, we report that obesity and diabetes resulted in increased macrophage infiltration in the colon. These macrophages exhibited the residency phenotype CX3CR1(hi)MHCII(hi) and were CD4-TIM4(-).During HFD, resident colonic LPM exhibited a lipid metabolism gene expression signature that overlapped that used to define lipid-associated macrophages (LAMs). Via single-cell RNA sequencing, we identified a sub-cluster of macrophages, increased in HFD, that were responsible for the LAM signature. Compared to other macrophages in the colon, these cells were charac-terized by elevated glycolysis, phagocytosis, and efferocytosis signatures. CX3CR1(hi)MHCII(hi) colonic resident LPMs had fewer lipid droplets (LDs) and decreased triacylglycerol (TG) content compared to equiv-alent cells in lean mice and exhibited increased phagocytic capacity, suggesting that HFD induces adaptive responses in LPMs to limit bacterial translocation. (AU)

• FAPESP's process: 17/05264-7 - Cell metabolism, microbiota and immune system: new paradigms in renal diseases physiopathology
• Grantee: Niels Olsen Saraiva Câmara
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 15/18121-4 - Relationship between obesity and intestinal lamina propria cells function in insulin resistance development
• Grantee: Angela Castoldi
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/00721-0 - Unraveling the metabolic demand of intestinal lamina propria macrophages and its role in Obesity and insulin resistance development
• Grantee: Angela Castoldi
• Support Opportunities: Scholarships in Brazil - Post-Doctoral