Dataset Information

High-Fat Diet Causes Rapid Loss of Intestinal Group 3 Innate Lymphoid Cells Through Microbiota-Driven Inflammation

ABSTRACT: Group 3 innate lymphoid cells (ILC3s) are critical sensory hubs to maintain intestinal immunity while adapting to environmental changes, including food intake and microbiota composition. Nutritional stress such as feeding on a high-fat diet (HFD) impairs ILC3s homeostasis, but the drivers underlying this phenotype remain elusive. Here, we found that intestinal ILC3s are depleted in overweight and obese humans, similarly to HFD-induced obese mice. However, we identified that ILC3s loss is not dependent on excessive calorie intake, weight gain, or glucose intolerance. Instead, we found that ILC3s impairment starts upon hours of HFD consumption, inducing microbial efflux. As a result, tissue-resident mononuclear phagocytes (MNPs) become proinflammatory, driving ILC3 cell death. We determined that the microbiota-driven stimulation overrides lipid-laden ILC3s ability to perform fatty acid oxidation, causing mitochondrial damage due to the accumulation of lipid peroxides. Collectively, our findings define the mechanism driving ILC3s maladaptation to fat-microbiota crosstalk and raise new considerations for understanding intestinal homeostasis and inflammation.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE317764 | GEO | 2026/05/26

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Carotenoids are naturally occurring pigments in plants responsible for the orange, yellow, and red color of fruits and vegetables. Carrots are one of the primary dietary sources of carotenoids. The biological activities of carotenoids in higher organisms are well documented in most tissues but not the large intestine. The gastrointestinal barrier acts as a line of defense against the systemic invasion of pathogenic bacteria, especially at the colonic level. Proteins involved in tight junction assembly between epithelial cells and mucus secretion from goblet cells are essential for maintaining intestinal barrier homeostasis. A high-fat diet can cause gut impairment by inducing barrier permeability, leading to low-grade chronic inflammation via metabolic endotoxemia. Our hypothesis for this study is that the dietary intake of carotenoid-rich foods can alleviate obesity-associated gut inflammation and strengthen the intestinal barrier function. Male C57BL/6J mice were randomized to one of four experimental diets for 20 weeks (n = 20 animals/group): Low-fat diet (LFD, 10% calories from fat), high-fat diet (HFD, 45% calories from fat), HFD with white carrot powder (HFD + WC), or HFD with orange carrot powder (HFD + OC). Colon tissues were harvested to analyze the biochemical effects of carotenoids in carrots. The distal sections were subjected to isobaric labeling-based quantitative proteomics in which tryptic peptides were labeled with tandem mass tags, followed by fractionation and LC-MS/MS analysis in an Orbitrap Eclipse Tribrid instrument. High-performance liquid chromatography results depicted that the HFD+WC pellets were carotenoid-deficient, and the HFD+OC pellets contained high concentrations of provitamin A carotenoids, specifically α-carotene and β-carotene. As a result of the quantitative proteomics, a total of 4410 differentially expressed proteins were identified. Intestinal barrier-associated proteins were highly upregulated in the HFD+OC group, particularly mucin-2 (MUC-2). Upon closer investigation into mucosal activity, other proteins related to MUC-2 functionality and tight junction management were upregulated by the HFD+OC dietary intervention. Carotenoid-rich foods may prevent high-fat diet-induced intestinal barrier disruption by promoting colonic mucus synthesis and secretion in mammalian organisms.

Dataset Information

High-Fat Diet Causes Rapid Loss of Intestinal Group 3 Innate Lymphoid Cells Through Microbiota-Driven Inflammation

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets