AMPK Mediate Energy Metabolism Transition and Lipid Autophagy in Mouse Liver Cells under Starvation Conditions

Purpose To explore the process of energy metabolism in mouse hepatocytes during starvation, revealing the changes of nutritional sensitivity, screening out the key pathways regulating autophagy and energy regulation in hepatocytes, and elucidating the mechanism of lipid degradation in response to energy mobilization.

Methods Inbred mice (C57/B6) were completely fasted for 0, 24 and 48 hours, the changes of blood glucose and body weight of mice were recorded according to time point. The liver tissues of mice in each group were detected by periodic acid-Schiff (PAS) staining and electron microscope observation, and the relative mRNA expression levels of related genes in glucose and lipid metabolism and autophagy were detected by q-PCR. Western-blot analysis was performed to detect the expression of key proteins in autophagy and energy-sensing AMPK pathway.

Results The expression level of protein LC3-Ⅱ/LC3-Ⅰ was extremely significantly increased, and the expression level of protein P62 was significantly decreased in the liver tissues of mice starved for 24 and 48 hours. Starvation induced the transformation of the main energy source in mouse hepatocytes, the mRNA expressions of autophagy genes ATG2A and PLIN2 were significantly up-regulated; the expressions mitochondrial membrane protein TOM20 and the proteins regulating energy metabolism and lipophagy (P-AMPK and P-FOXO1) were extremely significantly up-regulated. These results indicated that mitochondrial autophagy and lipophagy were induced by starvation treatment in the mouse liver cells.

Conclusion After 24 hours of starvation, the main energy source of mice changed from glucose metabolism to lipid metabolism. Starvation treatment may promote the lipophagic degradation of lipids stored in mouse hepatocytes by activating AMPK and FOXO1, releasing free fatty acid oxidation for energy supply.