TY - JOUR AB - Acetyl-coenzyme A carboxylase (ACC) is a critical regulator of fatty acid metabolism and represents a promising therapeutic target for metabolic diseases, including obesity, type 2 diabetes and non‑alcoholic fatty liver disease. Recently, a novel ACC inhibitor, PP‑7a, was developed by our group by utilizing a structure‑based drug design. In the present study, the pharmacological effects of PP‑7a on the metabolic dysregulation in mice with high‑fat diet (HFD)‑induced obesity and the underlying mechanisms were investigated. The inhibitory effect on ACC activities was confirmed by assessing the level of malonyl‑CoA, a product synthesized by the catalyzation of ACC. Following 16 weeks of being fed an HFD, the mice were administered PP‑7a (15, 45 or 75 mg/kg) for 4 weeks. The effects of PP‑7a on weight gain, glucose intolerance, hepatic lipid accumulation and the increase of serum triglyceride (TG), total cholesterol (TC) and free fatty acids (FFA) in mice were assessed. CP‑640186 was used as a positive control drug and administered in the same manner as PP‑7a. Chronic administration of PP‑7a lowered the malonyl‑CoA levels in liver and heart tissues of mice in the HFD group. In addition, HFD‑induced weight gain and glucose intolerance were improved by PP‑7a treatment in the mice fed the HFD. Furthermore, PP‑7a suppressed hepatic lipid accumulation and the increase in TG, TC and FFA levels. Taken together, these results suggest that ACC inhibition by PP‑7a may have a beneficial effect on metabolic dysregulation in obese mice. AD - Department of Pharmacy, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221004, P.R. China Center for Genetic Medicine, Maternity and Child Health Care Hospital Affiliated to Xuzhou Medical University, Xuzhou, Jiangsu 221004, P.R. China Jiangsu Province Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu 221004, P.R. China AU - Liu,Tianya AU - Gou,Lingshan AU - Yan,Shirong AU - Huang,Tonghui DA - 2020/07/01 DO - 10.3892/etm.2020.8700 EP - 529 IS - 1 JO - Exp Ther Med KW - PP‑7a acetyl‑coenzyme A carboxylase high‑fat diet‑induced obesity obesity lipid metabolism PY - 2020 SN - 1792-0981 1792-1015 SP - 521 ST - Inhibition of acetyl‑CoA carboxylase by PP‑7a exerts beneficial effects on metabolic dysregulation in a mouse model of diet‑induced obesity T2 - Experimental and Therapeutic Medicine TI - Inhibition of acetyl‑CoA carboxylase by PP‑7a exerts beneficial effects on metabolic dysregulation in a mouse model of diet‑induced obesity UR - https://doi.org/10.3892/etm.2020.8700 VL - 20 ER -