Sesamin alleviates lipid accumulation induced by oleic acid via PINK1/Parkin-mediated mitophagy in HepG2 cells.

Sesamin, a special compound present in sesame and sesame oil, has been reported a role in regulating lipid metabolism, while the underlying mechanisms remain unclear. Autophagy has been reported associated with lipid metabolism and regarded as a key modulator in liver steatosis. The present work aimed to investigate whether sesamin could exert its protective effects against lipid accumulation via modulating autophagy in HepG2 cells stimulated with oleic acid (OA). Cell viability was evaluated using the CCK-8 method, and triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein, cholesterol (LDL-C), alanine aminotransferase (ALT), along with aspartate aminotransferase (AST) were assessed by oil red O staining, transmission electron microscopy (TEM), and biochemical kits to investigate the lipid-lowering effects of sesamin. Differentially expressed genes were screened by RNA sequencing and validated using real-time quantitative PCR and Western blot. Autophagy and mitophagy related molecules were analyzed employing TEM, Western blot, and immunofluorescence. The data shows that in HepG2 cells stimulated by OA, sesamin reduces levels of TG, TC, LDL-C, ALT, and AST while elevating HDL-C, alleviates the lipid accumulation and improves fatty acid metabolism through modulating the levels of fat metabolism related genes including PCSK9, FABP1, CD36, and SOX4. Sesamin restores the suppressed autophagy in HepG2 cells caused by OA, which could be blocked by autophagy inhibitors. This indicates that sesamin improves fatty acid metabolism by enhancing autophagy levels, thereby mitigating the intracellular lipid accumulation. Furthermore, sesamin significantly enhances the mitophagy and improves mitochondrial homeostasis via activating the PINK/Parkin pathway. These data suggest that sesamin alleviates the excessive lipid accumulation in HepG2 caused by OA by restoring the impaired mitophagy via the PINK1/Parkin pathway, probably playing a preventive or therapeutic role in hepatic steatosis.

Influence of Proppant Size on the Proppant Embedment Depth.

Hydraulic fracturing is a well stimulation technique involving the fracturing of bedrock formations by a pressurized liquid, in which proppants are added to keep the fracture open after the fracturing operation. The scale discrepancy between the rock specimen and the proppant may bring deviations in the analysis of proppant embedment depth if the fluid-deteriorated formation is treated as an isotropic medium. This study tries to uncover the origins of these deviations through numerical and analytical analyses. The fluid-deteriorated formation is first modeled as a layered rock to obtain equivalent elastic parameters under isotropic conditions. Then, the equivalent parameters are used in the numerical modeling of proppant embedment. The numerical simulations indicate that the simplification of the fluid-deteriorated formation into an isotropic rock results in an underestimation of the proppant embedment depth, and this deviation increases with the scale contrast between rock specimens and proppants. Hertz contact theory is utilized to explain this deviation. As a promising technique, the nano/micro-indentation is also proposed to depict the fluid-deterioration effect along the depth. This study provides methods for the calibration of mechanical parameters of fluid-deteriorated rocks in the analysis of proppant embedment.