Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, 308 Ningxia Road, Qingdao, 266071, China.
Food Funct. 2022 Nov 28;13(23):12400-12411. doi: 10.1039/d2fo01934e.
Fructose has been reported to acutely elevate the circulating fibroblast growth factor 21 (FGF21) levels, which ultimately causes FGF21 resistance. FGF21 resistance is suggested to result in lipid metabolism disorder. Nicotinamide riboside (NR) can alleviate lipid metabolism disorder in mice. It is unknown whether NR supplementation would alleviate lipid metabolism disorder in high-fructose exposed mice improving FGF21 resistance. In this study, C57BL/6J mice were given 20% fructose solution for free drinking with the supplementation of NR in 400 mg kg day. The results showed that NR supplementation decreased the serum and hepatic lipid profile levels. The increase of lipid droplets in the liver and the size of adipose cells in WAT induced by a high-fructose diet were alleviated by the addition of NR. NR supplementation increased the NAD/NADH ratio and activated the SIRT1/NF-κB pathway. The down-regulation of NF-κB is accompanied by a decrease in inflammation, which may increase the expression of the FGF21 receptor complex, namely KLB and FGFR, then restore its downstream signaling cascade, including ERK phosphorylation and EGR1 and c-FOS expression, and ultimately improve FGF21 resistance. With the FGF21 function recovery, hepatic PGC-1α expression was up-regulated, and hepatic SREBP-1c expression was down-regulated, resulting in decreased lipogenesis. Furthermore, restoration of the FGF21 signaling pathway also led to increased expression of ATGL and HSL in WAT, which promotes lipolysis. In conclusion, we found that NR supplementation could ameliorate high-fructose-induced lipid metabolism disorder by improving FGF21 resistance in the liver and WAT, which may be related to the regulation of inflammation mediated by the SIRT1/NF-κB signaling pathway.
果糖已被报道可急性升高循环成纤维细胞生长因子 21（FGF21）水平，这最终导致 FGF21 抵抗。FGF21 抵抗被认为导致脂质代谢紊乱。烟酰胺核糖（NR）可减轻小鼠的脂质代谢紊乱。尚不清楚 NR 补充是否会改善暴露于高果糖的小鼠中的脂质代谢紊乱，从而改善 FGF21 抵抗。在这项研究中，C57BL/6J 小鼠自由饮用 20%果糖溶液，并补充 400mg/kg/天的 NR。结果表明，NR 补充降低了血清和肝脂质谱水平。NR 的添加减轻了高脂肪饮食引起的肝脏脂质滴增加和 WAT 中脂肪细胞的大小。NR 补充增加了 NAD/NADH 比值并激活了 SIRT1/NF-κB 途径。NF-κB 的下调伴随着炎症的减少，这可能会增加 FGF21 受体复合物（即 KLB 和 FGFR）的表达，从而恢复其下游信号级联，包括 ERK 磷酸化以及 EGR1 和 c-FOS 的表达，并最终改善 FGF21 抵抗。随着 FGF21 功能的恢复，肝 PGC-1α 的表达上调，肝 SREBP-1c 的表达下调，导致脂肪生成减少。此外，FGF21 信号通路的恢复还导致 WAT 中 ATGL 和 HSL 的表达增加，从而促进脂肪分解。总之，我们发现 NR 补充可通过改善肝脏和 WAT 中的 FGF21 抵抗来改善高果糖引起的脂质代谢紊乱，这可能与 SIRT1/NF-κB 信号通路介导的炎症调节有关。
