Rabbit Anti-Human PPARA (a.a. 61-170) Polyclonal antibody

Liver X receptor (LXR) activation can achieve satisfactory anti-atherosclerotic activity, but can also lead to the development of fatty liver and hypertriglyceridemia. In contrast, Notch inhibition can suppress both atherosclerosis and the hepatic accumulation of lipids. In the present study, we sought to assess whether combining LXR ligand agonists (T317) with Notch receptor inhibitors (DAPT) would lead to enhanced anti-atherosclerotic activity while overcoming the adverse events associated with LXR ligand agonist therapy. The impact of the combined T317 + DAPT therapeutic regimen on atherosclerosis, fatty liver development, and hypertriglyceridemia was assessed using ApoE deficient (ApoE(-/-)) mice. The results of this analysis suggested that DAPT was able to improve the anti-atherosclerotic activity of T317 without reducing the stability of lesion plaques while simultaneously reducing blood lipids in treated ApoE(-/-) mice. This combination T317 + DAPT treatment was also linked with a significant upregulation of ABCA1 and the stimulation of reverse cholesterol transport (RCT), as well as with decreases in the levels of intercellular cell adhesion molecule-1 (ICAM-1) and p-p65, and with altered M1/M2 macrophage proportions within atherosclerotic plaques. Importantly, DAPT was also able to reduce T317-mediated lipid accumulation within the liver owing to its ability to reduce SREBP-1 expression while simultaneously increasing that of Pi-AMPKa and PPARa. Together, our results suggest that administering Notch receptor inhibitors to ApoE(-/-) mice may be an effective means of enhancing the anti-atherosclerotic activity of LXR ligand agonists while simultaneously limiting associated fatty liver and hypertriglyceridemia development in these animals.

Introduction: Hypertriglyceridemia is among the multiple metabolic derangements seen in diabetes mellitus. Cornelian cherry (Cornus mas L.), belongs to the family Cornacea and has been shown to be helpful in treating hyperlipidemia. Aim: The study investigates mechanisms of action of dietary Cornelian Cherry fruit Dried Powder (CCDP) for ameliorating hypertriglyceridemia in diabetic rats. Materials and Methods: An experimental study with parallel controls was performed. Fifty six male adult rats were randomly assigned into 8 equal groups and treated as follows for 4 weeks. Negative control: Normal rats, basic diet; positive control: streptozotocin-induced diabetic rats, basic diet; T1 to T4 groups: diabetic rats fed with diets containing 0.25, 0.5, 1 and 2 g/ 100 g (BW) CCDP, respectively; T5: diabetic rats fed with basic diet plus 100 mg/kg( BW) of fenofibrate in drinking water and T6: normal rats fed with basic diet containing 1 g/100 g (BW) CCDP. Selected serum biochemical parameters, Lipoprotein Lipase (LPL) level as well as Adipose Tissue Hormone Sensitive Lipase (HSL) and Hepatic Peroxisome Proliferator-Activated Receptor Alpha (PPARa) levels were assayed. Analysis of data was performed by one-way ANOVA followed by Tukey's test with p<0.05 as the significant level. Results: Treatment with CCDP at all dosages as well as fenofibrate decreased serum triglycerides and VLDL levels as compared to positive control. Serum AST significantly decreased in T1, T3 and T4 groups as compared to positive control rats. Serum LPL levels in the diabetic positive control group decreased significantly as compared to negative control. Rats in T1, T2, T4 and T5 groups showed increased serum LPL levels as compared to positive control. No significant difference was observed in hepatic PPAR alpha levels among CCDP-treated and negative or positive controls. Positive control rats showed a significant decrease in adipose tissue HSL levels. Administration of CCDP in T3 group significantly increased HSL values as compared to positive control. CCDP in healthy rats did not change any of these parameters. Conclusion: Findings of the present study confirms positive effects of C. mas fruit on some liver function enzymes and hypertriglyceridemia and clarifies that increased serum LPL levels is at least partly responsible for hypotriglyceridemic effect of the fruit in rats with STZ-induced diabetes mellitus.