2. Academic Validation
  3. Glycophagy mediated glucose-induced changes of hepatic glycogen metabolism via OGT1-AKT1-FOXO1Ser238 pathway

Glycophagy mediated glucose-induced changes of hepatic glycogen metabolism via OGT1-AKT1-FOXO1Ser238 pathway

  • J Nutr Biochem. 2023 Mar 27;109337. doi: 10.1016/j.jnutbio.2023.109337.
Li-Xiang Wu 1,  Yi-Chuang Xu 1,  Kostas Pantopoulos 2,  Xiao-Ying Tan 1,  Xiao-Lei Wei 1,  Hua Zheng 1,  Zhi Luo 3
Affiliations

Affiliations

  • 1 Hubei Hongshan Laboratory, Fishery College, Huazhong Agriculture University, Wuhan 430070, China.
  • 2 Lady Davis Institute for Medical Research and Department of Medicine, McGill University, Montreal, H3T1E2, Quebec, Canada.
  • 3 Hubei Hongshan Laboratory, Fishery College, Huazhong Agriculture University, Wuhan 430070, China; Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266237, China. Electronic address: [email protected].
PMID: 36990368 DOI: 10.1016/j.jnutbio.2023.109337
Abstract

Glycophagy is the Autophagy degradation of glycogen. However, the regulatory mechanisms for glycophagy and glucose metabolism remain unexplored. Herein, we demonstrated that high-carbohydrate diet (HCD) and high glucose (HG) incubation induced glycogen accumulation, Akt1 expression and AKT1-dependent phosphorylation of forkhead transcription factor O1 (FOXO1) at Ser238 in the liver tissues and hepatocytes. The glucose-induced FOXO1 phosphorylation at Ser238 prevents FOXO1 entry into the nucleus and the recruitment to the gabarapl1 promoter, reduces the gabarapl1 promoter activity, and inhibits glycophagy and glucose production. The glucose-dependent O-GlcNAcylation of Akt1 by OGT1 enhances the stability of Akt1 protein and promotes its binding with FOXO1. Moreover, the glycosylation of Akt1 is crucial for promoting FOXO1 nuclear translocation and inhibiting glycophagy. Our studies elucidate a novel mechanism for glycophagy inhibition by high carbohydrate and glucose via OGT1-AKT1-FOXO1Ser238 pathway in the liver tissues and hepatocytes, which provides critical insights into potential intervention strategies for glycogen storage disorders in vertebrates, as well as human beings.

Keywords

Carbohydrate metabolism; Glycophagy; O-GlcNAcylation; Phosphorylation; Signaling pathway.

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