High dietary sugar intake exacerbates osteoarthritis by inducing TLR4-mediated inflammation in destabilized medial meniscus mice
Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B243
Abstract ID: 4595
Presenting Author:
Hyun-Jin Jang , Post-doc researcher at Jeju Natl. Univ.
Abstract:
In our previous study, we reported that a high sucrose (HS) diet exacerbates osteoarthritis (OA), hepatic inflammation and fibrosis in high-fat diet-fed OA animal model. Toll-like receptor 4 (TLR4), key player in inflammatory signaling, is crucial for liver inflammation, steatosis, and chondrocyte apoptosis in cartilage. However, the precise impact of HS-induced inflammation on OA severity through TLR4 remained unclear. To address this, both wild-type (WT) and TLR4 knock-out (TLR4 KO) mice underwent surgical destabilization of the medial meniscus (DMM) and exposed to either HS diets or corn starch-based control diets for 16-week. The HS diet intensified OA severity, synovitis, and crown-like structures (CLS) in adipose tissue with elevated total cholesterol and insulin levels in serum. Nevertheless, TLR4 KO resulted in: 1) reduced synovitis, 2) adipose size/mass, 3) CLS and inflammatory gene levels in adipose and hepatic tissue with decrease of bacterial 16S rRNA levels. Moreover, TLR4 KO showed 4) downregulated inflammatory genes expression with crypt depth in colon. Notably, next-generation sequencing (NGS) analysis in small intestine confirmed that TLR4 KO in HS-fed OA mice reduced 5) inflammatory bowel disease and IgA production signaling pathway, compared to HS-fed WT OA mice. In summary, excessive HS intake aggravates OA pathology through inflammation in the gut-liver-adipose tissue axis via TLR4-mediated immunomodulation.
The role of TLR4 in systemic inflammation induced by chronic sucrose exposure: insights from a destabilized medial meniscus mouse model
Category
Poster and Podium (Block Symposium)