title: Menopausal Status and Abdominal Obesity Are Significant Determinants of Hepatic Lipid Metabolism in Women.
abstract: BACKGROUND
  Android fat distribution (abdominal obesity) is associated with insulin resistance, hepatic steatosis, and greater secretion of large very low-density lipoprotein (VLDL) particles in men. Since abdominal obesity is becoming increasingly prevalent in women, we aimed to investigate the relationship between android fat and hepatic lipid metabolism in pre- and postmenopausal women.
  
  
  RESULTS
  We used a combination of stable isotope tracer techniques to investigate intrahepatic fatty acid synthesis and partitioning in 29 lean and 29 abdominally obese women (android fat/total fat 0.065 [0.02 to 0.08] and 0.095 [0.08 to 0.11], respectively). Thirty women were premenopausal aged 35 to 45 and they were matched for abdominal obesity with 28 postmenopausal women aged 55 to 65. As anticipated, abdominal obese women were more insulin resistant with enhanced hepatic secretion of large (404±30 versus 268±26 mg/kg lean mass, P<0.001) but not small VLDL (160±11 versus 142±13). However, postmenopausal status had a pronounced effect on the characteristics of small VLDL particles, which were considerably triglyceride-enriched (production ratio of VLDL2- triglyceride:apolipoprotein B 30±5.3 versus 19±1.6, P<0.05). In contrast to postmenopausal women, there was a tight control of hepatic fatty acid metabolism and triglyceride production in premenopausal women, whereby oxidation (rs=-0.49, P=0.006), de novo lipogenesis (rs=0.55, P=0.003), and desaturation (rs=0.48, P=0.012) were closely correlated with abdominal obesity-driven large VLDL-triglyceride secretion rate.
  
  
  CONCLUSIONS
  In women, abdominal obesity is a major driver of hepatic large VLDL particle secretion, whereas postmenopausal status was characterized by increased small VLDL particle size. These data provide a mechanistic basis for the hyperlipidemia observed in postmenopausal obesity.
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK (L.H., K.M., K.H., F.K., B.A.F.).
authors.forename: Leanne
authors.initials: L
authors.lastname: Hodson
authors.affiliation: Division of Cardiovascular Medicine, Oxford Centre for Clinical Magnetic Resonance Research, John Radcliffe Hospital, Oxford, UK (R.B., B.R.).
authors.forename: Rajarshi
authors.initials: R
authors.lastname: Banerjee
authors.affiliation: Division of Cardiovascular Medicine, Oxford Centre for Clinical Magnetic Resonance Research, John Radcliffe Hospital, Oxford, UK (R.B., B.R.).
authors.forename: Belén
authors.initials: B
authors.lastname: Rial
authors.affiliation: Centre for Endocrinology, Diabetes and Metabolism, School of Clinical & Experimental Medicine, University of Birmingham, UK (W.A.).
authors.forename: Wiebke
authors.initials: W
authors.lastname: Arlt
authors.affiliation: Department of Molecular and Clinical Medicine, University of Gothenburg, Sweden (M.A.) Department of Mathematical Sciences, University of Gothenburg, Sweden (M.A., J.B.).
authors.forename: Martin
authors.initials: M
authors.lastname: Adiels
authors.affiliation: Department of Mathematical Sciences, University of Gothenburg, Sweden (M.A., J.B.).
authors.forename: Jan
authors.initials: J
authors.lastname: Boren
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK (L.H., K.M., K.H., F.K., B.A.F.) Department of Experimental Physiology, Athens University School of Medicine, Athens, Greece (K.M.).
authors.forename: Kyriakoula
authors.initials: K
authors.lastname: Marinou
authors.affiliation: Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK (C.F., B.A.F.).
authors.forename: Ciaran
authors.initials: C
authors.lastname: Fisher
authors.affiliation: Department of Clinical Nutrition, Clinic of Clinical Service, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway (I.L.M.) Department of Cancer Research and Molecular Medicine, Faculty of Medicine, NTNU, Trondheim, Norway (I.L.M.).
authors.forename: Ingrid L
authors.initials: IL
authors.lastname: Mostad
authors.affiliation: Gloucestershire Diabetic Retinopathy Research Group, Cheltenham General Hospital, Gloucestershire, UK (I.M.S.).
authors.forename: Irene M
authors.initials: IM
authors.lastname: Stratton
authors.affiliation: Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia (H.R.B., D.C.C., G.F.W.) Faculty of Engineering, Computing and Mathematics, University of Western Australia, Perth, WA, Australia (H.R.B.).
authors.forename: P Hugh R
authors.initials: PH
authors.lastname: Barrett
authors.affiliation: Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia (H.R.B., D.C.C., G.F.W.).
authors.forename: Dick C
authors.initials: DC
authors.lastname: Chan
authors.affiliation: Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia (H.R.B., D.C.C., G.F.W.).
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Watts
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK (L.H., K.M., K.H., F.K., B.A.F.).
authors.forename: Karin
authors.initials: K
authors.lastname: Harnden
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK (L.H., K.M., K.H., F.K., B.A.F.) National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospital Trusts, Oxford, UK (F.K.).
authors.forename: Fredrik
authors.initials: F
authors.lastname: Karpe
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK (L.H., K.M., K.H., F.K., B.A.F.) Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK (C.F., B.A.F.).
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Fielding
mesh_terms: D050154:Adiposity; D000328:Adult; D000368:Aged; D053299:Apolipoprotein B-100 / Q000097:blood; D053305:Apolipoprotein C-III / Q000097:blood; D005227:Fatty Acids / Q000097:blood; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D007700:Kinetics; D050356:Lipid Metabolism; D050155:Lipogenesis; D008079:Lipoproteins, VLDL / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D010084:Oxidation-Reduction; D010316:Particle Size; D017698:Postmenopause / Q000378:metabolism*; D017697:Premenopause / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood; D015430:Weight Gain
chemical_list: C569471:APOB protein, human; D053299:Apolipoprotein B-100; D053305:Apolipoprotein C-III; D005227:Fatty Acids; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride
keywords: apolipoproteins; cholesterol; lipids; lipoproteins; menopause; women