Figure 2: Potential mechanisms for the reduction in risk factors for atherosclerosis by flavonoids. Both in vitro and in vivo data suggest that citrus flavonoids decrease macrophage uptake of oxidized LDL and macrophage CE accumulation and improve dyslipidemia. While the complete mechanisms have not been fully defined, the nuclear hormone receptors PPARα and PGC1α represent important molecular targets. The improvement in dyslipidemia can be linked to decreased VLDL secretion as hepatic lipid availability for storage or VLDL secretion is decreased as a consequence of PPAR-stimulated fatty acid oxidation. The oxidation of fatty acids by liver prevents ectopic lipid accumulation and improves both insulin sensitivity and glucose tolerance. Arrows indicate change in response to flavonoid treatment.