Year: 2026
Type: article
Abstract: Toll-like receptor 2 (TLR2) is an innate immune receptor linked to obesity primarily via NF-κB activation. Using a mouse model of overnutrition and in vitro TLR2 stimulation of human peripheral blood mononuclear cells, we show that lipids, advanced glycation end products, and low-density lipoproteins extend TLR2 signaling beyond NF-κB to promote Type I IFN production and signaling, establishing the relevance of this pathway to human obesity. This response was abolished by pharmacologic inhibition of the receptor for advanced glycation end products, which recognizes glycated proteins and lipids. In vivo dietary reversal, metformin, and tirzepatide each reduced diet-induced inflammation, but differed in their metabolic effects: dietary reversal reduced weight gain and LDL, tirzepatide reduced weight without lowering LDL, and metformin exerted anti-inflammatory effects independent of weight or LDL. These findings identify TLR2-Type I IFN signaling as a feature of diet-induced inflammation and highlight the diverse immunomodulatory effects of weight-management therapies.
Source: npj Metabolic Health and Disease
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,590
Funders: Arthritis National Research Foundation, Warren Alpert Foundation, Gilead Sciences, Lupus Research Alliance, Gilead Research Scholars, Manton Foundation, National Research Foundation, Deutsche Forschungsgemeinschaft, National Institutes of Health, European Regional Development Fund, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Perkin Fund
OpenAlex ID: W7172324655