Key result
A partial synthetic PPARƳ derivative significantly ameliorated aorta injury in HFD/STZ-induced T2D rats by decreasing inflammatory mediators and increasing microRNA126-5p and Pi3k/AKT pathway expression.
Why the study?
Endothelial dysfunction in T2D increases the risk of cardiovascular complications, prompting investigation into the efficacy of newly designed synthetic PPARalpha/gamma partial agonists in experimental T2D.
Does a partial synthetic PPARƳ derivative improve aorta injury and vascular inflammatory mediators in a rat model of HFD/STZ-induced T2D?
Does a partial synthetic PPARƳ derivative improve aorta injury and vascular inflammatory mediators in a rat model of HFD/STZ-induced T2D?
A novel partial synthetic PPARƳ derivative ameliorates vascular complications and aorta injury in a diabetic rat model by modulating inflammatory mediators and the miR-126-5p/Pi3k/AKT pathway.
Does not support clinical use in T2D; leaves open further preclinical development of PPARƳ derivatives for diabetic vasculopathy.
Type 2 diabetes mellitus (T2D) is a world wild health care issue marked by insulin resistance, a risk factor for the metabolic disorder that exaggerates endothelial dysfunction, increasing the risk of cardiovascular complications. Peroxisome proliferator-activated receptor PPAR) agonists have therapeutically mitigated hyperlipidemia and hyperglycemia in T2D patients. Therefore, we aimed to experimentally investigate the efficacy of newly designed synthetic PPARα/Ƴ partial agonists on a High-Fat Diet (HFD)/streptozotocin (STZ)-induced T2D. Female Wistar rats (200 ± 25 g body weight) were divided into four groups. The experimental groups were fed the HFD for three consecutive weeks before STZ injection (45 mg/kg/i.p) to induce T2D. Standard reference PPARƳ agonist pioglitazone and the partial synthetic PPARƳ (PIO; 20 mg/kg/BW, orally) were administered orally for 2 weeks after 72 h of STZ injection. The aorta tissue was isolated for biological ELISA, qRT-PCR, and Western blotting investigations for vascular inflammatory endothelial mediators endothelin-1 (ET-1), intracellular adhesion molecule 1 (ICAM-1), E-selectin, and anti-inflammatory vasoactive intestinal polypeptide (VIP), as well as microRNA126-5p and p-AKT/p-Pi3k/p-PDK-1/p-mTOR, endothelial Nitric Oxide Synthase (eNOS) immunohistochemical staining all are coupled with and histopathological examination. Our results revealed that HFD/STZ-induced T2D increased fasting blood glucose, ET-1, ICAM-1, E-selectin, and VIP levels, while decreasing the expression of both microRNA126-5p and p-AKT/p-Pi3k/p-PDK-1/p-mTOR phosphorylation. In contrast, the partial synthetic PPARƳ derivative evidenced a vascular alteration significantly more than reference PIO via decreasing (ET-1), ICAM-1, E-selectin, and VIP, along with increased expression of microRNA126-5p and p-AKT/p-Pi3k/p-PDK-1/p-mTOR. In conclusion, the partial synthetic PPARƳ derivative significantly affected HFD/STZ-induced T2D with vascular complications in the rat aorta.
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Ahmed et al. (2022) studied High-Fat Diet (HFD)/streptozotocin (STZ)-induced Type 2 Diabetes. Partial synthetic PPARƳ derivative vs. Pioglitazone (PIO) and untreated T2D control was evaluated on Vascular inflammatory endothelial mediators (ET-1, ICAM-1, E-selectin, VIP) and microRNA126-5p/p-AKT/p-Pi3k/p-PDK-1/p-mTOR expression. A partial synthetic PPARƳ derivative significantly ameliorated aorta injury in HFD/STZ-induced T2D rats by decreasing inflammatory mediators and increasing microRNA126-5p and Pi3k/AKT pathway expression.
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