Single nucleus multiomics reveals an early inflammatory response to high-fat diet in mouse islets.

Isabell Vs Ernst; Lasse Lehtonen; Freja L Nielsen; Morten F Ebbesen; Sille M Nilsson; Ann-Britt Marcher; Susanne Mandrup; Jesper Gs Madsen

doi:10.26508/lsa.202603840

PubMed · 42680559

Single nucleus multiomics reveals an early inflammatory response to high-fat diet in mouse islets.

Isabell Vs Ernst·Lasse Lehtonen·Freja L Nielsen·Morten F Ebbesen·Sille M Nilsson·Ann-Britt Marcher·Susanne Mandrup·Jesper Gs Madsen

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Abstract

In periods of sustained hyper-nutrition, pancreatic β-cells undergo functional compensation through transcriptional upregulation of gene programs driving insulin secretion. This adaptation is essential for maintaining systemic glucose homeostasis and metabolic health. Using single nuclei multiomics, we have mapped the early transcriptional adaptive mechanisms in murine islets of Langerhans exposed to high-fat diet (HFD) for 1 and 3 wk. We show that β-cells exhibit the largest transcriptional response to HFD, characterized by early activation of pro-inflammatory eRegulons and down-regulation of β-cell identity genes, particularly in a distinct subset of β-cells. These observations extend to humans, where the prevalence of an β-cells with a high inflammatory signature is increased in diabetes. Collectively, these observations point to cellular crosstalk through pro-inflammatory signaling as a central and early driver of β-cell dysfunction that limits the compensatory capacity of β-cells, which is closely linked to the development of diabetes.

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Animals Diet, High-Fat Mice Multiomics Islets of Langerhans Inflammation Insulin-Secreting Cells Male Mice, Inbred C57BL Insulin Insulin Secretion Cell Nucleus Gene Expression Regulation Journal Article

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Isabell Vs Ernst, Lasse Lehtonen, Freja L Nielsen, Morten F Ebbesen, Sille M Nilsson, Ann-Britt Marcher, Susanne Mandrup, Jesper Gs Madsen. 2026-09-01. Single nucleus multiomics reveals an early inflammatory response to high-fat diet in mouse islets.. https://doi.org/10.26508/lsa.202603840

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Journal Article resource Animals subject Cell Nucleus subject Diet, High-Fat subject Gene Expression Regulation subject Journal Article subject Male subject Mice subject Multiomics subject inflammation subject

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