Diet-induced obesity alters intestinal monocyte-derived and tissue-resident macrophages in female mice independent of TNF

Abstract

Macrophages are essential for homeostatic maintenance of the anti-inflammatory and tolerogenic intestinal environment, yet monocyte-derived macrophages can promote local inflammation. Pro-inflammatory macrophage accumulation within the intestines may contribute to the development of systemic chronic inflammation and immunometabolic dysfunction in obesity. Using a model of high fat diet-induced obesity in C57BL/6J female mice, we assessed intestinal permeability by in vitro and in vivo assays, and quantitated intestinal macrophages in ileum and colon tissues by multicolour flow cytometry after short (6 weeks), intermediate (12 weeks), and prolonged (18 weeks) diet allocation. We characterized monocyte-derived CD4-TIM4- and CD4+TIM4- macrophages, as well as tissue-resident CD4+TIM4+ macrophages. Diet-induced obesity had tissue and time-dependent effects on intestinal permeability, as well as monocyte and macrophage numbers, surface phenotype, and intracellular production of the cytokines IL-10 and TNF. We found that obese mice had increased paracellular permeability, in particular within the ileum, but this did not elicit recruitment of monocytes, nor a local pro-inflammatory response by monocyte-derived or tissue-resident macrophages, in either the ileum or colon. Proliferation of monocyte-derived and tissue-resident macrophages was also unchanged. Wildtype and TNF-/- littermate mice had similar intestinal permeability and macrophage population characteristics in response to diet-induced obesity. These data are unique from reported effects of diet-induced obesity on macrophages in metabolic tissues, as well as outcomes of acute inflammation within the intestines, and collectively indicate that TNF does not mediate effects of diet-induced obesity on intestinal monocyte-derived and tissue-resident intestinal macrophages in young female mice. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=152 SRC="FIGDIR/small/509732v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@140a3c8org.highwire.dtl.DTLVardef@c0d887org.highwire.dtl.DTLVardef@c7c70dorg.highwire.dtl.DTLVardef@1dd5404_HPS_FORMAT_FIGEXP M_FIG C_FIG