title: Sex-Specific Differences in Hepatic Fat Oxidation and Synthesis May Explain the Higher Propensity for NAFLD in Men.
abstract: OBJECTIVE
  In most populations a greater proportion of men have hepatic steatosis than women. Sex-specific differences in hepatic dietary fatty acid (FA) metabolism have not been well characterized. We compared fasting and postprandial hepatic FA synthesis (de novo lipogenesis [DNL]) and oxidation in men and women.
  
  
  METHODS
  Fasting and postprandial hepatic FA metabolism was studied in 22 healthy men (n = 11) and women with similar age, body mass index, and liver fat content using metabolic substrates labeled with stable-isotope tracers ((2)H2O and [U(13)C]palmitate). Dietary FA oxidation was assessed by appearance of (13)C into plasma 3-hydroxybutyrate and breath CO2 as markers of liver and whole-body FA oxidation, respectively.
  
  
  RESULTS
  Despite similar liver fat content, fasting and postprandial plasma triacylglycerol (TG) concentrations were significantly (P < .05) higher in men compared with women. The appearance of (13)C from dietary FA into plasma 3-hydroxybutyrate and breath CO2 was greater (P < .05) in women compared with men. Although the contribution of DNL into very low-density lipoprotein (VLDL)-TG was similar (∼ 10%) in the fasting state, there was a divergence in pattern over the course of the study, with men maintaining a higher contribution of DNL to VLDL-TG than women (P = .006 time x sex interaction).
  
  
  CONCLUSIONS
  The combination of lower dietary FA oxidation and a prolonged increase in DNL observed in men may represent partitioning of FA into esterification and storage pathways within the liver, leading to greater VLDL-TG production, and predispose to the sex difference in hepatic steatosis.
authors.affiliation: Oxford Centre for Diabetes, Endocrinology, and Metabolism (C.P., C.A.M., F.K., L.H.), Oxford Centre for Clinical Magnetic Resonance Research (M.P., R.B., S.N.), University of Oxford, Churchill Hospital, Oxford OX3 7LE, United Kingdom; and Translational Gastroenterology Unit (M.P.), John Radcliffe Hospital and National Institute for Health Research Oxford Biomedical Research Centre (F.K.), Oxford University Hospital Trusts, Oxford OX3 9DU, United Kingdom.
authors.forename: Camilla
authors.initials: C
authors.lastname: Pramfalk
authors.affiliation: Oxford Centre for Diabetes, Endocrinology, and Metabolism (C.P., C.A.M., F.K., L.H.), Oxford Centre for Clinical Magnetic Resonance Research (M.P., R.B., S.N.), University of Oxford, Churchill Hospital, Oxford OX3 7LE, United Kingdom; and Translational Gastroenterology Unit (M.P.), John Radcliffe Hospital and National Institute for Health Research Oxford Biomedical Research Centre (F.K.), Oxford University Hospital Trusts, Oxford OX3 9DU, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Pavlides
authors.affiliation: Oxford Centre for Diabetes, Endocrinology, and Metabolism (C.P., C.A.M., F.K., L.H.), Oxford Centre for Clinical Magnetic Resonance Research (M.P., R.B., S.N.), University of Oxford, Churchill Hospital, Oxford OX3 7LE, United Kingdom; and Translational Gastroenterology Unit (M.P.), John Radcliffe Hospital and National Institute for Health Research Oxford Biomedical Research Centre (F.K.), Oxford University Hospital Trusts, Oxford OX3 9DU, United Kingdom.
authors.forename: Rajarshi
authors.initials: R
authors.lastname: Banerjee
authors.affiliation: Oxford Centre for Diabetes, Endocrinology, and Metabolism (C.P., C.A.M., F.K., L.H.), Oxford Centre for Clinical Magnetic Resonance Research (M.P., R.B., S.N.), University of Oxford, Churchill Hospital, Oxford OX3 7LE, United Kingdom; and Translational Gastroenterology Unit (M.P.), John Radcliffe Hospital and National Institute for Health Research Oxford Biomedical Research Centre (F.K.), Oxford University Hospital Trusts, Oxford OX3 9DU, United Kingdom.
authors.forename: Catriona A
authors.initials: CA
authors.lastname: McNeil
authors.affiliation: Oxford Centre for Diabetes, Endocrinology, and Metabolism (C.P., C.A.M., F.K., L.H.), Oxford Centre for Clinical Magnetic Resonance Research (M.P., R.B., S.N.), University of Oxford, Churchill Hospital, Oxford OX3 7LE, United Kingdom; and Translational Gastroenterology Unit (M.P.), John Radcliffe Hospital and National Institute for Health Research Oxford Biomedical Research Centre (F.K.), Oxford University Hospital Trusts, Oxford OX3 9DU, United Kingdom.
authors.forename: Stefan
authors.initials: S
authors.lastname: Neubauer
authors.affiliation: Oxford Centre for Diabetes, Endocrinology, and Metabolism (C.P., C.A.M., F.K., L.H.), Oxford Centre for Clinical Magnetic Resonance Research (M.P., R.B., S.N.), University of Oxford, Churchill Hospital, Oxford OX3 7LE, United Kingdom; and Translational Gastroenterology Unit (M.P.), John Radcliffe Hospital and National Institute for Health Research Oxford Biomedical Research Centre (F.K.), Oxford University Hospital Trusts, Oxford OX3 9DU, United Kingdom.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Karpe
authors.affiliation: Oxford Centre for Diabetes, Endocrinology, and Metabolism (C.P., C.A.M., F.K., L.H.), Oxford Centre for Clinical Magnetic Resonance Research (M.P., R.B., S.N.), University of Oxford, Churchill Hospital, Oxford OX3 7LE, United Kingdom; and Translational Gastroenterology Unit (M.P.), John Radcliffe Hospital and National Institute for Health Research Oxford Biomedical Research Centre (F.K.), Oxford University Hospital Trusts, Oxford OX3 9DU, United Kingdom.
authors.forename: Leanne
authors.initials: L
authors.lastname: Hodson
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000378:metabolism; D000328:Adult; D000368:Aged; D002245:Carbon Dioxide / Q000378:metabolism; D004041:Dietary Fats / Q000378:metabolism; D005215:Fasting / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis; D005260:Female; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000096:biosynthesis*; D050155:Lipogenesis / Q000235:genetics; D008079:Lipoproteins, VLDL / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism*; D010084:Oxidation-Reduction; D010168:Palmitates / Q000378:metabolism; D019518:Postprandial Period; D012727:Sex Characteristics; D014280:Triglycerides / Q000097:blood
chemical_list: D004041:Dietary Fats; D005227:Fatty Acids; D008055:Lipids; D008079:Lipoproteins, VLDL; D010168:Palmitates; D014280:Triglycerides; D002245:Carbon Dioxide; D020155:3-Hydroxybutyric Acid