title: High-Density Lipoprotein Proteomic Composition, and not Efflux Capacity, Reflects Differential Modulation of Reverse Cholesterol Transport by Saturated and Monounsaturated Fat Diets.
abstract: Acute inflammation impairs reverse cholesterol transport (RCT) and reduces high-density lipoprotein (HDL) function in vivo. This study hypothesized that obesity-induced inflammation impedes RCT and alters HDL composition, and investigated if dietary replacement of saturated (SFA) for monounsaturated (MUFA) fatty acids modulates RCT.
  
  
  
  Macrophage-to-feces RCT, HDL efflux capacity, and HDL proteomic profiling was determined in C57BL/6j mice following 24 weeks on SFA- or MUFA-enriched high-fat diets (HFDs) or low-fat diet. The impact of dietary SFA consumption and insulin resistance on HDL efflux function was also assessed in humans. Both HFDs increased plasma (3)H-cholesterol counts during RCT in vivo and ATP-binding cassette, subfamily A, member 1-independent efflux to plasma ex vivo, effects that were attributable to elevated HDL cholesterol. By contrast, ATP-binding cassette, subfamily A, member 1-dependent efflux was reduced after both HFDs, an effect that was also observed with insulin resistance and high SFA consumption in humans. SFA-HFD impaired liver-to-feces RCT, increased hepatic inflammation, and reduced ABC subfamily G member 5/8 and ABC subfamily B member 11 transporter expression in comparison with low-fat diet, whereas liver-to-feces RCT was preserved after MUFA-HFD. HDL particles were enriched with acute-phase proteins (serum amyloid A, haptoglobin, and hemopexin) and depleted of paraoxonase-1 after SFA-HFD in comparison with MUFA-HFD.
  
  
  
  Ex vivo efflux assays validated increased macrophage-to-plasma RCT in vivo after both HFDs but failed to capture differential modulation of hepatic cholesterol trafficking. By contrast, proteomics revealed the association of hepatic-derived inflammatory proteins on HDL after SFA-HFD in comparison with MUFA-HFD, which reflected differential hepatic cholesterol trafficking between groups. Acute-phase protein levels on HDL may serve as novel biomarkers of impaired liver-to-feces RCT in vivo.
authors.affiliation: From Nutrigenomics Research Group (M.O., E.D., W.G., O.F., A. McMorrow, A. Murphy, C.L., D.J., H.M.R., F.C.M.), UCD Institute of Food and Health (M.R., M.G., E.G., L.B., H.M.R., F.C.M.), Diabetes Complications Research Centre (F.C.M.), UCD Conway Institute and School of Medicine, University College Dublin, Ireland; Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, PA (M.d.l.L.M.); and Cardiovascular Institute (M.P.R.) and Institute for Translational Medicine and Therapeutics (M.P.R.), University of Pennsylvania School of Medicine, Philadelphia.
authors.forename: Marcella
authors.initials: M
authors.lastname: O'Reilly
authors.affiliation: From Nutrigenomics Research Group (M.O., E.D., W.G., O.F., A. McMorrow, A. Murphy, C.L., D.J., H.M.R., F.C.M.), UCD Institute of Food and Health (M.R., M.G., E.G., L.B., H.M.R., F.C.M.), Diabetes Complications Research Centre (F.C.M.), UCD Conway Institute and School of Medicine, University College Dublin, Ireland; Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, PA (M.d.l.L.M.); and Cardiovascular Institute (M.P.R.) and Institute for Translational Medicine and Therapeutics (M.P.R.), University of Pennsylvania School of Medicine, Philadelphia.
authors.forename: Eugene
authors.initials: E
authors.lastname: Dillon
authors.affiliation: From Nutrigenomics Research Group (M.O., E.D., W.G., O.F., A. McMorrow, A. Murphy, C.L., D.J., H.M.R., F.C.M.), UCD Institute of Food and Health (M.R., M.G., E.G., L.B., H.M.R., F.C.M.), Diabetes Complications Research Centre (F.C.M.), UCD Conway Institute and School of Medicine, University College Dublin, Ireland; Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, PA (M.d.l.L.M.); and Cardiovascular Institute (M.P.R.) and Institute for Translational Medicine and Therapeutics (M.P.R.), University of Pennsylvania School of Medicine, Philadelphia.
authors.forename: Weili
authors.initials: W
authors.lastname: Guo
authors.affiliation: From Nutrigenomics Research Group (M.O., E.D., W.G., O.F., A. McMorrow, A. Murphy, C.L., D.J., H.M.R., F.C.M.), UCD Institute of Food and Health (M.R., M.G., E.G., L.B., H.M.R., F.C.M.), Diabetes Complications Research Centre (F.C.M.), UCD Conway Institute and School of Medicine, University College Dublin, Ireland; Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, PA (M.d.l.L.M.); and Cardiovascular Institute (M.P.R.) and Institute for Translational Medicine and Therapeutics (M.P.R.), University of Pennsylvania School of Medicine, Philadelphia.
authors.forename: Orla
authors.initials: O
authors.lastname: Finucane
authors.affiliation: From Nutrigenomics Research Group (M.O., E.D., W.G., O.F., A. McMorrow, A. Murphy, C.L., D.J., H.M.R., F.C.M.), UCD Institute of Food and Health (M.R., M.G., E.G., L.B., H.M.R., F.C.M.), Diabetes Complications Research Centre (F.C.M.), UCD Conway Institute and School of Medicine, University College Dublin, Ireland; Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, PA (M.d.l.L.M.); and Cardiovascular Institute (M.P.R.) and Institute for Translational Medicine and Therapeutics (M.P.R.), University of Pennsylvania School of Medicine, Philadelphia.
authors.forename: Aoibheann
authors.initials: A
authors.lastname: McMorrow
authors.affiliation: From Nutrigenomics Research Group (M.O., E.D., W.G., O.F., A. McMorrow, A. Murphy, C.L., D.J., H.M.R., F.C.M.), UCD Institute of Food and Health (M.R., M.G., E.G., L.B., H.M.R., F.C.M.), Diabetes Complications Research Centre (F.C.M.), UCD Conway Institute and School of Medicine, University College Dublin, Ireland; Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, PA (M.d.l.L.M.); and Cardiovascular Institute (M.P.R.) and Institute for Translational Medicine and Therapeutics (M.P.R.), University of Pennsylvania School of Medicine, Philadelphia.
authors.forename: Aoife
authors.initials: A
authors.lastname: Murphy
authors.affiliation: From Nutrigenomics Research Group (M.O., E.D., W.G., O.F., A. McMorrow, A. Murphy, C.L., D.J., H.M.R., F.C.M.), UCD Institute of Food and Health (M.R., M.G., E.G., L.B., H.M.R., F.C.M.), Diabetes Complications Research Centre (F.C.M.), UCD Conway Institute and School of Medicine, University College Dublin, Ireland; Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, PA (M.d.l.L.M.); and Cardiovascular Institute (M.P.R.) and Institute for Translational Medicine and Therapeutics (M.P.R.), University of Pennsylvania School of Medicine, Philadelphia.
authors.forename: Claire
authors.initials: C
authors.lastname: Lyons
authors.affiliation: From Nutrigenomics Research Group (M.O., E.D., W.G., O.F., A. McMorrow, A. Murphy, C.L., D.J., H.M.R., F.C.M.), UCD Institute of Food and Health (M.R., M.G., E.G., L.B., H.M.R., F.C.M.), Diabetes Complications Research Centre (F.C.M.), UCD Conway Institute and School of Medicine, University College Dublin, Ireland; Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, PA (M.d.l.L.M.); and Cardiovascular Institute (M.P.R.) and Institute for Translational Medicine and Therapeutics (M.P.R.), University of Pennsylvania School of Medicine, Philadelphia.
authors.forename: Daniel
authors.initials: D
authors.lastname: Jones
authors.affiliation: From Nutrigenomics Research Group (M.O., E.D., W.G., O.F., A. McMorrow, A. Murphy, C.L., D.J., H.M.R., F.C.M.), UCD Institute of Food and Health (M.R., M.G., E.G., L.B., H.M.R., F.C.M.), Diabetes Complications Research Centre (F.C.M.), UCD Conway Institute and School of Medicine, University College Dublin, Ireland; Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, PA (M.d.l.L.M.); and Cardiovascular Institute (M.P.R.) and Institute for Translational Medicine and Therapeutics (M.P.R.), University of Pennsylvania School of Medicine, Philadelphia.
authors.forename: Miriam
authors.initials: M
authors.lastname: Ryan
authors.affiliation: From Nutrigenomics Research Group (M.O., E.D., W.G., O.F., A. McMorrow, A. Murphy, C.L., D.J., H.M.R., F.C.M.), UCD Institute of Food and Health (M.R., M.G., E.G., L.B., H.M.R., F.C.M.), Diabetes Complications Research Centre (F.C.M.), UCD Conway Institute and School of Medicine, University College Dublin, Ireland; Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, PA (M.d.l.L.M.); and Cardiovascular Institute (M.P.R.) and Institute for Translational Medicine and Therapeutics (M.P.R.), University of Pennsylvania School of Medicine, Philadelphia.
authors.forename: Michael
authors.initials: M
authors.lastname: Gibney
authors.affiliation: From Nutrigenomics Research Group (M.O., E.D., W.G., O.F., A. McMorrow, A. Murphy, C.L., D.J., H.M.R., F.C.M.), UCD Institute of Food and Health (M.R., M.G., E.G., L.B., H.M.R., F.C.M.), Diabetes Complications Research Centre (F.C.M.), UCD Conway Institute and School of Medicine, University College Dublin, Ireland; Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, PA (M.d.l.L.M.); and Cardiovascular Institute (M.P.R.) and Institute for Translational Medicine and Therapeutics (M.P.R.), University of Pennsylvania School of Medicine, Philadelphia.
authors.forename: Eileen
authors.initials: E
authors.lastname: Gibney
authors.affiliation: From Nutrigenomics Research Group (M.O., E.D., W.G., O.F., A. McMorrow, A. Murphy, C.L., D.J., H.M.R., F.C.M.), UCD Institute of Food and Health (M.R., M.G., E.G., L.B., H.M.R., F.C.M.), Diabetes Complications Research Centre (F.C.M.), UCD Conway Institute and School of Medicine, University College Dublin, Ireland; Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, PA (M.d.l.L.M.); and Cardiovascular Institute (M.P.R.) and Institute for Translational Medicine and Therapeutics (M.P.R.), University of Pennsylvania School of Medicine, Philadelphia.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Brennan
authors.affiliation: From Nutrigenomics Research Group (M.O., E.D., W.G., O.F., A. McMorrow, A. Murphy, C.L., D.J., H.M.R., F.C.M.), UCD Institute of Food and Health (M.R., M.G., E.G., L.B., H.M.R., F.C.M.), Diabetes Complications Research Centre (F.C.M.), UCD Conway Institute and School of Medicine, University College Dublin, Ireland; Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, PA (M.d.l.L.M.); and Cardiovascular Institute (M.P.R.) and Institute for Translational Medicine and Therapeutics (M.P.R.), University of Pennsylvania School of Medicine, Philadelphia.
authors.forename: Margarita
authors.initials: M
authors.lastname: de la Llera Moya
authors.affiliation: From Nutrigenomics Research Group (M.O., E.D., W.G., O.F., A. McMorrow, A. Murphy, C.L., D.J., H.M.R., F.C.M.), UCD Institute of Food and Health (M.R., M.G., E.G., L.B., H.M.R., F.C.M.), Diabetes Complications Research Centre (F.C.M.), UCD Conway Institute and School of Medicine, University College Dublin, Ireland; Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, PA (M.d.l.L.M.); and Cardiovascular Institute (M.P.R.) and Institute for Translational Medicine and Therapeutics (M.P.R.), University of Pennsylvania School of Medicine, Philadelphia.
authors.forename: Muredach P
authors.initials: MP
authors.lastname: Reilly
authors.affiliation: From Nutrigenomics Research Group (M.O., E.D., W.G., O.F., A. McMorrow, A. Murphy, C.L., D.J., H.M.R., F.C.M.), UCD Institute of Food and Health (M.R., M.G., E.G., L.B., H.M.R., F.C.M.), Diabetes Complications Research Centre (F.C.M.), UCD Conway Institute and School of Medicine, University College Dublin, Ireland; Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, PA (M.d.l.L.M.); and Cardiovascular Institute (M.P.R.) and Institute for Translational Medicine and Therapeutics (M.P.R.), University of Pennsylvania School of Medicine, Philadelphia.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Roche
authors.affiliation: From Nutrigenomics Research Group (M.O., E.D., W.G., O.F., A. McMorrow, A. Murphy, C.L., D.J., H.M.R., F.C.M.), UCD Institute of Food and Health (M.R., M.G., E.G., L.B., H.M.R., F.C.M.), Diabetes Complications Research Centre (F.C.M.), UCD Conway Institute and School of Medicine, University College Dublin, Ireland; Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, PA (M.d.l.L.M.); and Cardiovascular Institute (M.P.R.) and Institute for Translational Medicine and Therapeutics (M.P.R.), University of Pennsylvania School of Medicine, Philadelphia. fiona.mcgillicuddy@ucd.ie.
authors.forename: Fiona C
authors.initials: FC
authors.lastname: McGillicuddy
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002784:Cholesterol / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects*; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects; D005227:Fatty Acids / Q000008:administration & dosage* / Q000009:adverse effects; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008075:Lipoproteins, HDL / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009765:Obesity / Q000209:etiology / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D055815:Young Adult
chemical_list: D004041:Dietary Fats; D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D008075:Lipoproteins, HDL; D002784:Cholesterol
keywords: cholesterol, HDL; inflammation; lipoproteins; obesity; proteome; reverse cholesterol transport