Stearic acid induces proinflammatory cytokine production partly through activation of lactate-HIF1α pathway in chondrocytes

• Published in: Scientific reports Vol. 5; no. 1; p. 13092
• Main Authors: Miao, Hongming, Chen, Liang, Hao, Lijun, Zhang, Xuan, Chen, Yujuan, Ruan, Zhihua, Liang, Houjie
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14.08.2015; Nature Publishing Group
• Subjects: 631/80/86/2365; 692/163/2743/316; Animals; Cells, Cultured; Chondrocytes - cytology; Chondrocytes - immunology; Cytokines - immunology; Diet, High-Fat - methods; Humanities and Social Sciences; Hypoxia-Inducible Factor 1, alpha Subunit - immunology; Inflammation Mediators - immunology; Lactic Acid - immunology; Male; Mice; Mice, Inbred C57BL; multidisciplinary; Science; Signal Transduction - immunology; Stearic Acids - immunology; Vascular Endothelial Growth Factor A - immunology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep13092

The biomechanics stress and chronic inflammation in obesity are causally linked to osteoarthritis. However, the metabolic factors mediating obesity-related osteoarthritis are still obscure. Here we scanned and identified at least two elevated metabolites (stearic acid and lactate) from the plasma of diet-induced obese mice. We found that stearic acid potentiated LDH-a-dependent production of lactate, which further stabilized HIF1α protein and increased VEGF and proinflammatory cytokine expression in primary mouse chondrocytes. Treatment with LDH-a and HIF1α inhibitors notably attenuated stearic acid-or high fat diet-stimulated proinflammatory cytokine production in vitro and in vivo . Furthermore, positive correlation of plasma lactate, cartilage HIF1α and cytokine levels with the body mass index was observed in subjects with osteoarthritis. In conclusion, saturated free fatty acid induced proinflammatory cytokine production partly through activation of a novel lactate-HIF1α pathway in chondrocytes. Our findings hold promise of developing novel clinical strategies for the management of obesity-related diseases such as osteoarthritis.