Abstract:
Excessive fat deposition leads to obesity and cardiovascular diseases with abnormal metabolism. Pantothenic acid (PA) is a major B vitamin required for energy metabolism. However, the effect of PA on lipid metabolism and obesity has not been explored. We investigated the effects and molecular mechanism of PA on fat accumulation as well as the influence of adipogenic marker genes in both adult male mice and primary adipocytes. First, we demonstrated that PA attenuates weight gain in mice fed high-fat diet (HFD). Besides, PA supplementation substantially improved glucose tolerance and lipid metabolic disorder in obese mice. Furthermore, PA significantly inhibited white adipose tissue (WAT) deposition as well as fat droplets visualized by magnification in both chow and HFD group. More importantly, PA obviously suppressed the mRNA levels of CD36, IL-6, and TNF-α to alleviate inflammation and reduced the levels of PPARγ, aP2, and C/EBPα genes that are related to lipid metabolism in inguinal white adipose tissue (ing-WAT) and epididymal white adipose tissue (ei-WAT). In vitro, PA supplementation showed a lower lipid droplet aggregation as well as reduced expression levels of adipogentic genes. Finally, we identified that PA inhibits the phosphorylation levels of p38 and JNK in murine primary adipocytes. Collectively, our data demonstrated for the first time that PA attenuates lipid metabolic disorder as well as fat deposition by JNK/p38 MAPK signaling pathway.
摘要:
过多的脂肪沉积导致肥胖和代谢异常的心血管疾病。泛酸(PA)是能量代谢所需的主要B族维生素。然而,PA对脂质代谢和肥胖的影响尚未被研究。我们研究了PA对成年雄性小鼠和原代脂肪细胞脂肪积累的影响和分子机制以及成脂标记基因的影响。首先,我们证明了PA可以减轻高脂饮食(HFD)小鼠的体重增加。此外,补充PA可显著改善肥胖小鼠的葡萄糖耐量和脂质代谢紊乱。此外,PA显着抑制白色脂肪组织(WAT)沉积以及放大显示的脂肪滴在食物和HFD组中。更重要的是,PA明显抑制CD36,IL-6和TNF-α的mRNA水平,减轻炎症反应,降低PPARγ的水平,aP2和C/EBPα基因与腹股沟白色脂肪组织(ing-WAT)和附睾白色脂肪组织(ei-WAT)中的脂质代谢有关。体外,PA补充显示出较低的脂滴聚集以及脂肪生成基因的表达水平降低。最后,我们发现PA抑制小鼠原代脂肪细胞中p38和JNK的磷酸化水平。总的来说,我们的数据首次证明PA通过JNK/p38MAPK信号通路减轻了脂质代谢紊乱和脂肪沉积.