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Article History

Received: 25 March 2024

Accepted: 9 August 2024

First Online: 6 November 2024

Acknowledgements

: We acknowledge the help of R. Mecham (Washington University) with measurements of vessel compliance in Cd36 −/− mice and the help of S. C. Beeman (Arizona State University) with ASL MRI of microvascular perfusion in the kidney.Dr. David Wasserman died on 20 June 2024 from health issues. David was the Annie Mary Lyle Professor of Molecular Physiology and Biophysics at Vanderbilt University, he contributed groundbreaking research to our understanding of the factors that regulate glucose metabolism by various organs. He also founded and directed the Mouse Metabolic Phenotyping Center, which became an international resource for studying mouse metabolism. This manuscript is dedicated to his memory as a wonderful scientist, collaborator and friend.

: The RNAseq data generated in this study have been deposited in the NCBI Gene Expression Omnibus ( ) under accession code GSE235988 ( ). Microarray data are available as ESM Table . All other data analysed for this study are available from the corresponding author upon request.

: We acknowledge support from the National Institute of Health (RO1DK111175 [NAA, CAS, NNA]); NHLBI R01HL157584 [CAS]; NHLBI R01 HL045095 [IJG, NAA]), Clinical Translational Science Award (CAS) and assistance from Vanderbilt Institute for Clinical and Translational Sciences (5UL1TR002243-03) and Washington University Nutrition and Obesity Center (NORC, P30 DK056341).

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

: CAS and NNA designed the human studies. CAS recruited participants, performed the insulin clamps and CAS and NNA analysed the data. VSP designed, performed and analysed all cell studies. DHW and IMW designed, performed and analysed the mice insulin clamps and insulin flux experiments. DS designed, performed and analysed the mice metabolic studies. TP performed the human genotyping, the vessel compliance assays, the immunohistochemistry and gene expression studies, and analysed the RNAseq and microarray data. CAS, VSP, TP, DS, IMW and DHW reviewed and edited the manuscript. NNA and IJG contributed to study design and to data interpretation and critically reviewed the manuscript. ERG designed the PrediXcan approach to query the Vanderbilt BioVu patient biobank, collected and analysed the PrediXcan data and edited the manuscript. All authors approved the final manuscript version. NAA conceived and designed the study, analysed the data, wrote the manuscript and is the guarantor of this work.