AMPK Mediates Energy Metabolism Transformation and Lipid Autophagy in Mouse Liver Cells under Starvation Conditions

ZHANG Xiaoyin; SU Hongding; MAO Shengyi; YANG Chang; JIAO Deling; WANG Jing; WEI Hongjiang; ZHAO Hongye

doi:10.12101/j.issn.1004-390X(n).202401023

JOURNAL OF YUNNAN AGRICULTURAL UNIVERSITY（Natural Science） > 2024 > 39(6): 48-58. > DOI: 10.12101/j.issn.1004-390X(n).202401023

ZHANG Xiaoyin, SU Hongding, MAO Shengyi, et al. AMPK Mediates Energy Metabolism Transformation and Lipid Autophagy in Mouse Liver Cells under Starvation Conditions[J]. JOURNAL OF YUNNAN AGRICULTURAL UNIVERSITY（Natural Science）, 2024, 39(6): 48-58. DOI: 10.12101/j.issn.1004-390X(n).202401023

Citation:

PDF (3138 KB)

AMPK Mediates Energy Metabolism Transformation and Lipid Autophagy in Mouse Liver Cells under Starvation Conditions

ZHANG Xiaoyin^{1, 2,},
SU Hongding^{1, 2,},
MAO Shengyi¹,
YANG Chang^{1, 3},
JIAO Deling^{1, 4},
WANG Jing^{1, 3},
WEI Hongjiang^{1, 3, 4},
ZHAO Hongye^{1, 4, ,}

1.
Key Laboratory of Gene Editing and Xenotransplantation for Miniature Pigs in Yunnan Province, Yunnan Agricultural University, Kunming 650201, China
2.
College of Plant Protection, Yunnan Agricultural University, Kunming 650201, China
3.
Faculty of Animal Science and Technology, Yunnan Agricultural University, Kunming 650201, China
4.
College of Animal Medicine, Yunnan Agricultural University, Kunming 650201, China

More Information

Received Date: January 23, 2024
Revised Date: October 22, 2024
Accepted Date: October 26, 2024
Available Online: October 30, 2024
Published Date: December 05, 2024

Graphical Abstract

Abstract

Abstract

Purpose
To explore the process of energy metabolism in mouse hepatocytes during starvation, revealing the changes in 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 acids for oxidation to supply energy.
- starvation,
- energy metabolism transformation,
- lipophagy,
- AMP-activated protein kinase (AMPK)

FullText(HTML)

References (24)

References

[1]	ESMAEILIAN Y, HELA F, BILDIK G, et al. Autophagy regulates sex steroid hormone synthesis through lysosomal degradation of lipid droplets in human ovary and testis[J]. Cell Death & Disease, 2023, 14(5): 342. DOI: 10.1038/s41419-023-05864-3.
[2]	OHSUMI Y. Historical landmarks of autophagy research[J]. Cell Research, 2014, 24(1): 9. DOI: 10.1038/cr.2013.169.
[3]	XU C C, FAN J L. Links between autophagy and lipid droplet dynamics[J]. Journal of Experimental Botany, 2022, 73(9): 2848. DOI: 10.1093/jxb/erac003.
[4]	JUSOVIĆ M, STARIČ P, JOVIČIĆ J E, et al. The combined inhibition of autophagy and diacylglycerol acyltransferase-mediated lipid droplet biogenesis induces cancer cell death during acute amino acid starvation[J]. Cancers, 2023, 15(19): 4857. DOI: 10.3390/cancers15194857.
[5]	FAN J L, YU L H, XU C C. Dual role for autophagy in lipid metabolism in Arabidopsis[J]. The Plant Cell, 2019, 31(7): 1598. DOI: 10.1105/tpc.19.00170.
[6]	CHEN L P, JIN Y, WU J, et al. Lipid droplets: a cellular organelle vital for thermogenesis[J]. International Journal of Biological Sciences, 2022, 18(16): 6176. DOI: 10.7150/ijbs.77051.
[7]	LIU M X, XU L, ZHU P F, et al. Two-photon excited red-green “discoloration” bioprobes for monitoring lipid droplets and lipid droplet-lysosomal autophagy[J]. Journal of Materials Chemistry B, 2023, 11(14): 3186. DOI: 10.1039/D2TB02621J.
[8]	CHUNG J, PARK J, LAI Z W, et al. The troyer syndrome protein spartin mediates selective autophagy of lipid droplets[J]. Nature Cell Biology, 2023, 25(8): 1101. DOI: 10.1038/s41556-023-01178-w.
[9]	PARK J M, LEE D H, KIM D H. Redefining the role of AMPK in autophagy and the energy stress response[J]. Nature Communications, 2023, 14(1): 2994. DOI: 10.1038/s41467-023-38401-z.
[10]	YAO Y, JIA W K, ZENG X F, et al. FAT10 combined with miltefosine inhibits mitochondrial apoptosis and energy metabolism in hypoxia-induced H9C2 cells by regulating the PI3K/AKT signaling pathway[J]. Evidence-Based Complementary and Alternative Medicine, 2022, 2022: 4388919. DOI: 10.1155/2022/4388919.
[11]	LU J Y, HUANG J Q, ZHAO S S, et al. FOXO1 is a critical switch molecule for autophagy and apoptosis of sow endometrial epithelial cells caused by oxidative stress[J]. Oxidative Medicine and Cellular Longevity, 2021, 2021: 1172273. DOI: 10.1155/2021/1172273.
[12]	史琳娜, 王柯, 邓玉娣, 等. 脂噬对脂质代谢的调节作用及其分子机制[J]. 南方医科大学学报, 2019, 39(7): 867. DOI: 10.12122/j.issn.1673-4254.2019.07.19.
[13]	BOSCH M, SÁNCHEZ-ÁLVAREZ M, FAJARDO A, et al. Mammalian lipid droplets are innate immune hubs integrating cell metabolism and host defense[J]. Science, 2020, 370(6514): 309. DOI: 10.1126/science.aay8085.
[14]	EASTMAN S W, YASSAEE M, BIENIASZ P D. A role for ubiquitin ligases and Spartin/SPG20 in lipid droplet turnover[J]. The Journal of Cell Biology, 2009, 184(6): 881. DOI: 10.1083/jcb.200808041.
[15]	PU M M, ZHENG W H, ZHANG H T, et al. ORP8 acts as a lipophagy receptor to mediate lipid droplet turnover[J]. Protein & Cell, 2023, 14(9): 653. DOI: 10.1093/procel/pwac063.
[16]	AGROTIS A, PENGO N, BURDEN J J, et al. Redundancy of human ATG4 protease isoforms in autophagy and LC3/GABARAP processing revealed in cells[J]. Autophagy, 2019, 15(6): 976. DOI: 10.1080/15548627.2019.1569925.
[17]	FRUDD K, BURGOYNE T, BURGOYNE J R. Oxidation of Atg3 and Atg7 mediates inhibition of autophagy[J]. Nature Communications, 2018, 9(1): 95. DOI: 10.1038/s41467-017-02352-z.
[18]	NODA N N. Atg2 and Atg9: intermembrane and interleaflet lipid transporters driving autophagy[J]. Biochimica Et Biophysica Acta: Molecular and Cell Biology of Lipids, 2021, 1866(8): 158956. DOI: 10.1016/j.bbalip.2021.158956.
[19]	KIMMEL A R, BRASAEMLE D L, MCANDREWS-Hill M, et al. Adoption of PERILIPIN as a unifying nomenclature for the mammalian PAT-family of intracellular lipid storage droplet proteins[J]. Journal of Lipid Research, 2010, 51(3): 468. DOI: 10.1194/jlr.R000034.
[20]	FANG C L, LIU S J, YANG W Q, et al. Exercise ameliorates lipid droplet metabolism disorder by the PLIN2-LIPA axis-mediated lipophagy in mouse model of non-alcoholic fatty liver disease[J]. BBA-Molecular Basis of Disease, 2024, 1870(3): 167045. DOI: 10.1016/j.bbadis.2024.167045.
[21]	HERZIG S, SHAW R J. AMPK: guardian of metabolism and mitochondrial homeostasis[J]. Nature Reviews Molecular Cell Biology, 2018, 19(2): 121. DOI: 10.1038/nrm.2017.95.
[22]	LIN S C, HARDIE D G. AMPK: sensing glucose as well as cellular energy status[J]. Cell Metabolism, 2018, 27(2): 299. DOI: 10.1016/j.cmet.2017.10.009.
[23]	ZHANG L Q, ZHANG Z G, LI C B, et al. S100A11 promotes liver steatosis via FOXO1-mediated autophagy and lipogenesis[J]. Cellular and Molecular Gastroenterology and Hepatology, 2021, 11(3): 697. DOI: 10.1016/j.jcm-gh.2020.10.006.
[24]	DAI L N, LI S M, LI X, et al. Propofol inhibits the malignant development of osteosarcoma U2OS cells via AMPK/FOXO1-mediated autophagy[J]. Oncology Letters, 2022, 24(3): 310. DOI: 10.3892/ol.2022.13430.

Cited By

Get Citation

PDF

XML

Article views (580) PDF downloads (10)

Turn off MathJax

Article Contents

Abstract

References

AMPK Mediates Energy Metabolism Transformation and Lipid Autophagy in Mouse Liver Cells under Starvation Conditions

Abstract

References

Catalog

Export File

Citation

Format

Content