| There is growing evidence that people who consume more fruits and vegetables have a lower prevalence of important risk factors for cardiovascular disease (CVD), including hyperlipidemia, hypertension, obesity, and type 2 diabetes, The protective effect of consuming fruits and vegetables may be attributed to a number of unique bioactive compounds known as phytochemicals. In the present studies, we investigated the potential role and mechanism of action of plant flavonoids and indole-based compounds, on lipid metabolism, including apolipoprotein B (apoB), using ElepG2 cells (in vitro) and a hamster model of metabolic syndrome (in vivo).;Using HepG2 cells, the flavonoids, xanthohumol (XN) and taxifolin (TX) were shown to decrease apoB secretion into culture medium dose dependently up to 43% at 15 mumol/L and 63% at 200 mumol/L, respectively. The secretion of TG was also significantly reduced. These effects were mediated via the inhibition of key lipogenic enzymes, including diacylglycerol acyltransferase (DGAT) and microsomal triglyceride transfer protein (MTP). Similarly, indole-3-carbinol (I-3-C), derived from cruciferous vegetables, reduced apoB secretion into the media dose dependently up to 56% at 100 mumol/L. Significant decreases in cellular lipid synthesis, including TG and cholesterol esters (CE), and their associated biosynthetic enzymes were observed in cells treated with I-3-C. The effect on fatty acid synthase (FASN) was shown to be mediated by sterol regulatory element binding protein (SREBP)-1, an important transcription factor involved in fatty acid synthesis.;To extrapolate these findings in vivo, a preventive approach was adopted in which induction of the metabolic syndrome and hyperlipidemia through high-fructose feeding was done concurrently with I-3-C supplementation (100 and 200 mg/Kg b.w./day). Serum TG was reduced by I-3-C treatment (by 40% at 100 mg/Kg b.w./day) as compared to the untreated fructose-controls. I-3-C supplementation also prevented the accumulation of lipids in the liver by decreasing the activity of DGAT and MTP. Interestingly, I-3-C supplementation also improved the insulin resistance index indicating that I-3-C may also be used to treat diabetes.;We hope that our studies may ultimately provide new information which could lead to human dietary intervention trials in the prevention and/or treatment of the hyperlipidemia associated with the metabolic syndrome. |
