Department of Chemistry and Life Science, College of Bioresource Sciences, Nihon University, Fujisawa, Kanagawa, Japan.
Department of Applied Life Science, Graduate School of Bioresource Sciences, Nihon University, Fujisawa, Kanagawa, Japan.
Biosci Biotechnol Biochem. 2021 Apr 24;85(5):1104-1113. doi: 10.1093/bbb/zbab030.
Protein malnutrition promotes hepatic lipid accumulation in growing animals. In these animals, fibroblast growth factor 21 (FGF21) rapidly increases in the liver and circulation and plays a protective role in hepatic lipid accumulation. To investigate the mechanism by which FGF21 protects against liver lipid accumulation under protein malnutrition, we determined whether upregulated FGF21 promotes the thermogenesis or secretion of very-low-density lipoprotein (VLDL)-triacylglycerol (TAG). The results showed that protein malnutrition decreased VLDL-TAG secretion, but the upregulation of FGF21 did not oppose this effect. In addition, protein malnutrition increased expression of the thermogenic gene uncoupling protein 1 in inguinal white adipose and brown adipose tissue in an FGF21-dependent manner. However, surgically removing inguinal white adipose tissue did not affect liver triglyceride levels in protein-malnourished mice. These data suggest that FGF21 stimulates thermogenesis under protein malnutrition, but this is not the causative factor underlying the protective role of FGF21 against liver lipid accumulation.
蛋白质营养不良会促进生长中的动物肝脏脂质堆积。在这些动物中，成纤维细胞生长因子 21（FGF21）在肝脏和循环中迅速增加，并在肝脏脂质堆积中发挥保护作用。为了研究 FGF21 在蛋白质营养不良下如何防止肝脏脂质堆积的机制，我们确定上调的 FGF21 是否促进极低密度脂蛋白（VLDL）-三酰甘油（TAG）的产热或分泌。结果表明，蛋白质营养不良会降低 VLDL-TAG 的分泌，但 FGF21 的上调并没有对抗这种作用。此外，蛋白质营养不良以 FGF21 依赖的方式增加了腹股沟白色脂肪组织和棕色脂肪组织中解偶联蛋白 1 的产热基因表达。然而，手术切除腹股沟白色脂肪组织并不影响蛋白质营养不良小鼠的肝甘油三酯水平。这些数据表明，FGF21 在蛋白质营养不良下刺激产热，但这不是 FGF21 防止肝脏脂质积累的保护作用的因果因素。
