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06-06-2017 | Image

Figure 3: Two-hit model of OA pathogenesis involving lipopolysaccharide.

The induction of obesity by a high-fat diet could lead to site-specific cartilage strains, which, along with injury, could be triggers for osteoarthritis (OA). Factors contributing to elevation of levels of systemic lipopolysaccharide include a high-fat diet with secondary insulin resistance, Gram-negative bacterial overload in the gastrointestinal tract, and a fatty liver with impairment of lipopolysaccharide clearance. High levels of systemic lipopolysaccharide can activate the innate immune system via macrophage stimulation, which can exacerbate the process of OA triggered by excess cartilage strain. A high level of physical activity can mitigate the effects of lipopolysaccharide, through enhancement of systemic levels of HDL cholesterol and lipopolysaccharide clearance, and through reduction of Toll-like receptor 4 activation to reduce the inflammatory response to lipopolysaccharide. NAFLD, nonalcoholic fatty-liver disease.

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