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Article History

Received: 25 May 2023

Accepted: 7 August 2023

First Online: 15 September 2023

Acknowledgements

: We thank N. Bovin, Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, for help with the synthesis of glucose–biotin–PAA; J. Kim and R. Friedline, UMass Chan Medical School and NIDDK Mouse Metabolic Phenotyping Centers (), for help with hyperinsulinaemic–euglycaemic clamps; V. K. Thomas and J. Zhang, URMC Center for Advanced Light Microscopy and Nanoscopy, for help with microscopy; K. Welle and K. Swovick, University of Rochester Mass Spectrometry Resource Laboratory for proteomics analyses; M. Schaff, ProteoGenix, for help with the SPRi technique; S. Espitia, HDBiosciences, for the ADGRL1 signalling assays. The EE ANCOVA analysis done for this work was provided by the NIDDK Mouse Metabolic Phenotyping Centers using their Energy Expenditure Analysis page () and supported by grants DK076169 and DK115255.

: All data are available in the main text or the supplemental materials. The reagents and mouse model used in this study are available via material transfer agreement addressed to the corresponding author.

: This study received funding from the following sources: National Institutes of Health grants DK124619, DK122190 and DK113115 to KHC; Startup funds, Department of Medicine, University of Rochester to KHC; The Del Monte Institute for Neuroscience Pilot Research Award, University of Rochester to KHC; University Research Award, Office of the Vice President for Research, University of Rochester to KHC; National Institutes of Health instrument grant OD025242 to University of Rochester Mass Spectrometry Resource Laboratory; National Institutes of Health grant DK093000 to the University of Massachusetts Chan Medical School; Stark Neurosciences Research Institute, Indiana University to BKA.

: The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.

: KHC conceived the study, designed and performed experiments, analysed results, prepared graphs and figures, and wrote and edited the manuscript. SB performed experiments including microscopy, analysed results, prepared graphs and figures, and edited the manuscript. TSF, DJS and MUR performed experiments, analysed results and edited the manuscript. LMdSC helped with experiments involving ovariectomy for intellectual content and edited the manuscript. GVDP and BKA performed electrophysiological recordings, analysed the results and edited the manuscript. JR, LB and AD genotyped mice, performed experiments including the sectioning of the mouse brain, and edited the manuscript. All authors approved the final version of the manuscript. KHC is the guarantor of this work.