PMID- 36079859 OWN - NLM STAT- MEDLINE DCOM- 20220912 LR - 20220919 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 14 IP - 17 DP - 2022 Aug 31 TI - Vasorin Deletion in C57BL/6J Mice Induces Hepatocyte Autophagy through Glycogen-Mediated mTOR Regulation. LID - 10.3390/nu14173600 [doi] LID - 3600 AB - Abnormal vasorin (Vasn) expression occurs in multiple diseases, particularly liver cancers. Vasn knockout (KO) in mice causes malnutrition, a shortened life span, and decreased physiological functions. However, the causes and underlying mechanisms remain unknown. Here, we established Vasn KO C57BL/6J mice by using the CRISPR/Cas9 system. The animals were weighed, and histology, immunohistochemistry, electronic microscopy, and liver function tests were used to examine any change in the livers. Autophagy markers were detected by Western blotting. MicroRNA (miRNA) sequencing was performed on liver samples and analyses to study the signaling pathway altered by Vasn KO. Significant reductions in mice body and liver weight, accompanied by abnormal liver function, liver injury, and reduced glycogen accumulation in hepatocytes, were observed in the Vasn KO mice. The deficiency of Vasn also significantly increased the number of autophagosomes and the expression of LC3A/B-II/I but decreased SQSTM1/p62 levels in hepatocytes, suggesting aberrant activation of autophagy. Vasn deficiency inhibited glycogen-mediated mammalian target of rapamycin (mTOR) phosphorylation and activated Unc-51-like kinase 1 (ULK1) signaling, suggesting that Vasn deletion upregulates hepatocyte autophagy through the mTOR-ULK1 signaling pathway as a possible cause of diminished life span and health. Our results indicate that Vasn is required for the homeostasis of liver glycogen metabolism upstream of hepatocyte autophagy, suggesting research values for regulating Vasn in pathways related to liver physiology and functions. Overall, this study provides new insight into the role of Vasn in liver functionality. FAU - Yang, Lichao AU - Yang L AD - School of Public Health, Guangxi Medical University, Nanning 530021, China. AD - Laboratory Animal Center, Guangxi Medical University, Nanning 530021, China. FAU - Cheng, Xiaojing AU - Cheng X AD - School of Public Health, Guangxi Medical University, Nanning 530021, China. AD - Life Sciences Institute, Guangxi Medical University, Nanning 530021, China. FAU - Shi, Wei AU - Shi W AUID- ORCID: 0000-0003-0368-1887 AD - Laboratory Animal Center, Guangxi Medical University, Nanning 530021, China. FAU - Li, Hui AU - Li H AD - School of Public Health, Guangxi Medical University, Nanning 530021, China. FAU - Zhang, Qi AU - Zhang Q AD - Laboratory Animal Center, Guangxi Medical University, Nanning 530021, China. FAU - Huang, Shiping AU - Huang S AD - School of Public Health, Guangxi Medical University, Nanning 530021, China. FAU - Huang, Xuejing AU - Huang X AD - Laboratory Animal Center, Guangxi Medical University, Nanning 530021, China. FAU - Wen, Sha AU - Wen S AD - Laboratory Animal Center, Guangxi Medical University, Nanning 530021, China. FAU - Gan, Ji AU - Gan J AD - Laboratory Animal Center, Guangxi Medical University, Nanning 530021, China. FAU - Liao, Zhouxiang AU - Liao Z AD - School of Public Health, Guangxi Medical University, Nanning 530021, China. FAU - Sun, Junming AU - Sun J AD - Laboratory Animal Center, Guangxi Medical University, Nanning 530021, China. FAU - Liang, Jinning AU - Liang J AD - Laboratory Animal Center, Guangxi Medical University, Nanning 530021, China. FAU - Ouyang, Yiqiang AU - Ouyang Y AD - Laboratory Animal Center, Guangxi Medical University, Nanning 530021, China. FAU - He, Min AU - He M AD - School of Public Health, Guangxi Medical University, Nanning 530021, China. AD - Laboratory Animal Center, Guangxi Medical University, Nanning 530021, China. AD - Key Laboratory of High-Incidence-Tumor Prevention & Treatment, Guangxi Medical University, Ministry of Education, Nanning 530021, China. LA - eng GR - 32000865/National Natural Science Foundation of China/ GR - 81760612/National Natural Science Foundation of China/ GR - ZY1949025/Guangxi Natural Science Foundation/ GR - AB16380184/Guangxi Natural Science Foundation/ GR - 43XB3783XB/China Postdoctoral Science Foundation/ GR - GKE-ZZ202108/the Program of key Laboratory of High-Incidence-Tumor Prevention and Treatment (Guangxi Medical University), Ministry of Education, China/ GR - GKE-ZZ202002/the Program of key Laboratory of High-Incidence-Tumor Prevention and Treatment (Guangxi Medical University), Ministry of Education, China/ GR - GKE2019-03/the Program of key Laboratory of High-Incidence-Tumor Prevention and Treatment (Guangxi Medical University), Ministry of Education, China/ PT - Journal Article DEP - 20220831 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (Membrane Proteins) RN - 0 (Vasn protein, mouse) RN - 9005-79-2 (Glycogen) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Animals MH - *Apoptosis Regulatory Proteins/genetics MH - Autophagy/genetics MH - *Glycogen MH - Hepatocytes/metabolism MH - *Membrane Proteins/genetics MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - *TOR Serine-Threonine Kinases/genetics/metabolism PMC - PMC9460126 OTO - NOTNLM OT - ULK1 OT - autophagy OT - glycogen OT - mTOR OT - vasorin (Vasn) COIS- The authors declare no conflict of interest. EDAT- 2022/09/10 06:00 MHDA- 2022/09/14 06:00 PMCR- 2022/08/31 CRDT- 2022/09/09 01:25 PHST- 2022/07/30 00:00 [received] PHST- 2022/08/20 00:00 [revised] PHST- 2022/08/29 00:00 [accepted] PHST- 2022/09/09 01:25 [entrez] PHST- 2022/09/10 06:00 [pubmed] PHST- 2022/09/14 06:00 [medline] PHST- 2022/08/31 00:00 [pmc-release] AID - nu14173600 [pii] AID - nutrients-14-03600 [pii] AID - 10.3390/nu14173600 [doi] PST - epublish SO - Nutrients. 2022 Aug 31;14(17):3600. doi: 10.3390/nu14173600.