The CAMERA trial is funded by a project grant from the Chief Scientist Office, Scotland (CZB/4/613). D.P. is supported by a University of Oxford British Heart Foundation Centre of Research Excellence Senior Transition Fellowship (RE/13/1/30181). N.S. and P.W. acknowledge support from a BHF Centre of Excellence award (COE/RE/18/6/34217). We thank P. Barker, K. Burling and other members of the Cambridge Biochemical Assay Laboratory (CBAL). This project is supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. A.P.C., D. Rimmington, J.A.T., I.C., Y.C.L.T. and G.S.H.Y. are supported by the Medical Research Council (MRC Metabolic Diseases Unit (MC_UU_00014/1)). Mouse studies in Cambridge are supported by S. Grocott and the Disease Model Core, with pathology support from J. Warner and the Histopathology Core (MRC Metabolic Diseases Unit (MC_UU_00014/5) and Wellcome Trust Strategic Award (100574/Z/12/Z). D.B.S. and S.O. are supported by the Wellcome Trust (WT 107064 and WT 095515/Z/11/Z), the MRC Metabolic Disease Unit (MC_UU_00014/1) and The National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre and NIHR Rare Disease Translational Research Collaboration. We thank J. Jones and other members of the Histopathology and ISH Core Facility, Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre. D. Ron is supported by a Wellcome Trust Principal Research Fellowship (Wellcome 200848/Z/16/Z) and a Wellcome Trust Strategic Award to the Cambridge Institute for Medical Research (Wellcome 100140). A.V.-P., S.R.-C. and S.V. are supported by the BHF (RG/18/7/33636) and MRC (MC_UU_00014/2). A.M. is supported by a studentship from the Experimental Medicine Training Initiative/AstraZeneca. R.A.T. and L.V. are supported by an ERC advanced grant NewChol and core support from the Wellcome Trust and Medical Research Council to the Wellcome–Medical Research Council Cambridge Stem Cell Institute. M.Y., D.A.G., E.L.M., F.M.G. and F.R. are supported by the MRC (MC_UU_00014/3) and Wellcome Trust (106262/Z/14/Z and 106263/Z/14/Z). M.Y. is supported by a BBSRC-DTP studentship. A.R.K., R.R.E. and K.S.N. are supported by NIH Grants R21 AG60139, UL1 TR000135 and T32DK007352 and acknowledge K. Klaus for technical assistance. N.J.W. is supported by the MRC (MC_UU_12015/1) and is an NIHR Senior Investigator. We acknowledge J. Luan for statistical assistance. CHOP-null mice were a gift from J. Goodall.