Chongqing Key Lab of Medicinal Chemistry & Molecular Pharmacology, Chongqing University of Technology, Chongqing 400054, China.
Food Funct. 2021 May 11;12(9):4165-4175. doi: 10.1039/d0fo02654a.
Obesity is a serious health issue as it is a social burden and the main risk factor for other metabolic diseases. Increasing evidence indicates that a high-fat diet (HFD) is the key factor for the development of obesity, but the key genes and their associated molecular mechanisms are still not fully understood. In this study, we performed integrated bioinformatic analysis and identified that fructose-1,6 biphosphatase 2 (FBP2) was involved in free fatty acids (FFAs)-induced lipid droplet accumulation in hepatocytes and HFD-induced obesity in mice. Our data showed that palmitate (PA) and oleic acid (OA) induced the expression of FBP2 in time- and dose-dependent manners, and accelerated the development of lipid droplets in LO2 human normal liver cells. In HFD-fed C57BL/6 mice, accompanied by insulin resistance and lipid droplet accumulation, the mRNA and protein levels of FBP2 in the livers also increased significantly. The results from the methylation sequencing PCR (MSP) and bisulfite specific PCR (BSP) indicated that PA/OA induced the demethylation of the FBP2 gene promoter in LO2 cells. Moreover, betaine, a methyl donor, attenuated the expression of the FBP2 gene, the accumulation of lipid droplets, and the expression of perilipin-2, a biomarker of lipid droplets, in LO2 cells. All these findings revealed that FBP2 might be involved in HFD-induced obesity, and it is of interest to investigate the role of FBP2 in the treatment and prevention of obesity and its associated complications.
肥胖是一个严重的健康问题，因为它是一种社会负担，也是其他代谢性疾病的主要风险因素。越来越多的证据表明，高脂肪饮食（HFD）是肥胖发展的关键因素，但关键基因及其相关的分子机制仍未完全阐明。在这项研究中，我们进行了综合的生物信息学分析，确定果糖-1,6-二磷酸酶 2（FBP2）参与了游离脂肪酸（FFAs）诱导的肝细胞脂滴积累和 HFD 诱导的肥胖小鼠模型。我们的数据表明，软脂酸（PA）和油酸（OA）以时间和剂量依赖的方式诱导 FBP2 的表达，并加速 LO2 人正常肝细胞中脂滴的形成。在 HFD 喂养的 C57BL/6 小鼠中，伴随着胰岛素抵抗和脂滴积累，肝脏中 FBP2 的 mRNA 和蛋白水平也显著增加。甲基化测序 PCR（MSP）和亚硫酸氢盐特异性 PCR（BSP）的结果表明，PA/OA 诱导 LO2 细胞中 FBP2 基因启动子的去甲基化。此外，甲基供体甜菜碱可减弱 LO2 细胞中 FBP2 基因的表达、脂滴的积累以及脂滴标志物 perilipin-2 的表达。这些发现表明 FBP2 可能参与了 HFD 诱导的肥胖，研究 FBP2 在肥胖及其相关并发症的治疗和预防中的作用具有重要意义。
