Dyrk1b promotes hepatic lipogenesis by bypassing canonical insulin signaling and directly activating mTORC2 in mice

• Published in: The Journal of clinical investigation Vol. 132; no. 3; pp. 1 - 19
• Main Authors: Bhat, Neha, Narayanan, Anand, Fathzadeh, Mohsen, Kahn, Mario, Zhang, Dongyan, Goedeke, Leigh, Neogi, Arpita, Cardone, Rebecca L., Kibbey, Richard G., Fernandez-Hernando, Carlos, Ginsberg, Henry N., Jain, Dhanpat, Shulman, Gerald I., Mani, Arya
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.02.2022
• Subjects: Animals; Biomedical research; Calories; Cellular signal transduction; Development and progression; Dyrk Kinases; Fatty liver; Fibrosis; Genetic aspects; Glycogen; Health aspects; Hepatology; High fat diet; Humans; Hyperlipidemia; Insulin; Insulin - metabolism; Insulin resistance; Kinases; Lipids; Lipogenesis; Liver - metabolism; Liver diseases; Mechanistic Target of Rapamycin Complex 2 - genetics; Mechanistic Target of Rapamycin Complex 2 - metabolism; Medical research; Medicine, Experimental; Metabolic syndrome; Metabolism; Mice; Mutation; Phosphorylation; Physiological aspects; Protein kinase C; Protein kinases; Protein Serine-Threonine Kinases - genetics; Protein Serine-Threonine Kinases - metabolism; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - metabolism; Signal Transduction; Steatosis; Sucrose; Synthesis; Therapeutic targets; United States; Obesity; Metabolism; Protein kinases; Hepatology; Insulin signaling

Mutations in Dyrk1b are associated with metabolic syndrome and nonalcoholic fatty liver disease in humans. Our investigations showed that DYRK1B levels are increased in the liver of patients with nonalcoholic steatohepatitis (NASH) and in mice fed with a high-fat, high-sucrose diet. Increasing Dyrk1...