{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["113(26)"],"submitter":["Chen L"],"pubmed_abstract":["Tre-2/USP6, BUB2, cdc16 domain family member 1 (the TBC domain is the GTPase activating protein domain) (TBC1D1) is a Rab GTPase activating protein that is phosphorylated on Ser(231) by the AMP-activated protein kinase (AMPK) in response to intracellular energy stress. However, the in vivo role and importance of this phosphorylation event remains unknown. To address this question, we generated a mouse model harboring a TBC1D1(Ser231Ala) knockin (KI) mutation and found that the KI mice developed obesity on a normal chow diet. Mechanistically, TBC1D1 is located on insulin-like growth factor 1 (IGF1) storage vesicles, and the KI mutation increases endocrinal and paracrinal/autocrinal IGF1 secretion in an Rab8a-dependent manner. Hypersecretion of IGF1 causes increased expression of lipogenic g"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pagination":["7219-24"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4932950"],"repository":["biostudies-literature"],"pubmed_title":["Disruption of the AMPK-TBC1D1 nexus increases lipogenic gene expression and causes obesity in mice via promoting IGF1 secretion."],"pmcid":["PMC4932950"],"pubmed_authors":["Chen Q","Sheng Y","MacKintosh C","Quan C","Zhou S","Sakamoto K","Chen L","Rong P","Chen S","Xie B","Zhu S","Wang HY"],"additional_accession":[]},"is_claimable":false,"name":"Disruption of the AMPK-TBC1D1 nexus increases lipogenic gene expression and causes obesity in mice via promoting IGF1 secretion.","description":"Tre-2/USP6, BUB2, cdc16 domain family member 1 (the TBC domain is the GTPase activating protein domain) (TBC1D1) is a Rab GTPase activating protein that is phosphorylated on Ser(231) by the AMP-activated protein kinase (AMPK) in response to intracellular energy stress. However, the in vivo role and importance of this phosphorylation event remains unknown. To address this question, we generated a mouse model harboring a TBC1D1(Ser231Ala) knockin (KI) mutation and found that the KI mice developed obesity on a normal chow diet. Mechanistically, TBC1D1 is located on insulin-like growth factor 1 (IGF1) storage vesicles, and the KI mutation increases endocrinal and paracrinal/autocrinal IGF1 secretion in an Rab8a-dependent manner. Hypersecretion of IGF1 causes increased expression of lipogenic g","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Jun","modification":"2026-05-05T15:07:08.278Z","creation":"2019-03-27T02:17:35Z"},"accession":"S-EPMC4932950","cross_references":{"pubmed":["27307439"],"doi":["10.1073/pnas.1600581113"]}}