Nervonic acid is a very long-chain monounsaturated fatty acid with physiological effects including promoting nerve regeneration and regulating lipid metabolism. It has wide application potential in fields such as infant formula, health foods, and medicine. This review summarizes the distribution characteristics of natural nervonic acid from different sources such as animals, plants and microorganisms, focusing on recent progress in the biosynthesis of nervonic acid using oleaginous microorganisms such as Yarrowia lipolytica and Rhodosporidium toruloides. We shed light on the industrial prospects of its biomanufacturing. On this basis, we address the development trends and future prospects of nervonic acid enrichment and purification, efficacy evaluation and product development. This review aims to provide a theoretical basis for the biological manufacturing of nervonic acid and offer a scientific reference for its industrial production and high-value applications.

The modulation of lysosome-dependent autophagy as a critical protective mechanism affecting the pathogenesis of the non-alcoholic fatty liver disease (NAFLD) is becoming a growing area of concern. The current research was designed to evaluate the effect of plant sterol ester of α-linolenic acid (PS-ALA) on lysosomal function and autophagy in preventing the occurrence of hepatic steatosis using in vivo and in vitro models. Our result showed that treatment with PS-ALA significantly alleviated lipid and free cholesterol (FC) accumulation in a high-fat and high-cholesterol diet (HFCD) feeding mice and reduced the levels of FC, free fatty acid, and triglyceride by 66.7%, 70.4%, and 58.3% in oleic acid/cholesterol (OA/Cho)-treated HepG2 cells. In addition, we found that HFCD or OA/Cho damaged lysosomal function and blocked autophagy characteristics by increased LC3II and p62 accumulation. Administration of PS-ALA significantly promoted lysosome biogenesis, alleviated the damage of lysosomes, activated autophagy, and accelerate lysosome-dependent lipid degradation in OA/Cho-induced cells. Further molecular mechanism study revealed that PS-ALA intervention reduced the expression level of phosphorylation mTORC1 by 34% in the liver and induced subsequent nuclear translocation of TFEB. Activation of mTORC1 by MHY1485 markedly abolished PS-ALA-induced lysosome biogenesis and autophagy in OA/Cho-induced cells, leading to lipid accumulation. Our findings support the suitability of PS-ALA as a therapeutic strategy for NAFLD upon its beneficial effect on lysosomal function and autophagy via inhibiting mTORC1 signaling.