Figure 8
Proposed models for FFA/lactate-mediated HIF1α-cytokine axis in obesity-related osteoarthritis.
Briefly, circulatory levels of saturate FFA are increased in diet-induced obesity. Saturated FFA could stimulate proinflammatory cytokine production in chondrocytes directly through TLR4. Meanwhile, the elevated FFA stimulates LDH-a-dependent lactate production in chondrocytes and perhaps also in other cells. Consequently, the levels of circulatory lactate are also increased in response to HFD treatment. The increased lactate would stabilize and activate HIF-1α protein in chondrocytes to stimulate the production of VEGF and proinflammatory cytokines. In summary, saturated FFA could stimulate proinflammatory cytokine production in chondrocytes directly through TLR4 or LDHa-lactate-HIF1α pathway, which provides a potential molecular mechanism linking obesity to chronic inflammation in osteoarthritis.
