title: Fasting Plasma Insulin Concentrations Are Associated With Changes in Hepatic Fatty Acid Synthesis and Partitioning Prior to Changes in Liver Fat Content in Healthy Adults.
abstract: Resistance to the action of insulin affects fatty acid delivery to the liver, fatty acid synthesis and oxidation within the liver, and triglyceride export from the liver. To understand the metabolic consequences of hepatic fatty acid synthesis, partitioning, oxidation, and net liver fat content in the fasted and postprandial states, we used stable-isotope tracer methodologies to study healthy men and women with varying degrees of insulin resistance before and after consumption of a mixed meal. Subjects were classified as being normoinsulinemic (NI) (fasting plasma insulin <11.2 mU/L, n = 18) or hyperinsulinemic (HI) (fasting plasma insulin >11.2 mU/L, n = 19). Liver fat content was similar between HI and NI individuals, despite HI subjects having marginally more visceral fat. However, de novo lipogenesis was higher and fatty acid oxidation was lower in HI individuals compared with NI subjects. These data suggest that metabolic pathways promoting fat accumulation are enhanced in HI but, paradoxically, without any significant effect on liver fat content when observed in healthy people. This is likely to be explained by increased triglyceride secretion as observed by hypertriglyceridemia.
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, U.K.
authors.forename: Camilla
authors.initials: C
authors.lastname: Pramfalk
authors.affiliation: Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, Oxford, U.K. Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, U.K.
authors.forename: Michael
authors.initials: M
authors.lastname: Pavlides
authors.affiliation: Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, Oxford, U.K.
authors.forename: Rajarshi
authors.initials: R
authors.lastname: Banerjee
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, U.K.
authors.forename: Catriona A
authors.initials: CA
authors.lastname: McNeil
authors.affiliation: Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, Oxford, U.K.
authors.forename: Stefan
authors.initials: S
authors.lastname: Neubauer
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, U.K. National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospital Trusts, Oxford, U.K.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Karpe
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, U.K. leanne.hodson@ocdem.ox.ac.uk.
authors.forename: Leanne
authors.initials: L
authors.lastname: Hodson
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000502:physiology; D005215:Fasting; D005227:Fatty Acids / Q000096:biosynthesis*; D005234:Fatty Liver / Q000378:metabolism; D005260:Female; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology*; D050356:Lipid Metabolism / Q000502:physiology; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D005227:Fatty Acids; D007328:Insulin; D006003:Glycogen