title: Diabetic and dyslipidaemic morbidly obese exhibit more liver alterations compared with healthy morbidly obese.
abstract: OBJECTIVE
  To study the origin of fat excess in the livers of morbidly obese (MO) individuals, we analysed lipids and lipases in both plasma and liver and genes involved in lipid transport, or related with, in that organ.
  
  
  METHODS
  Thirty-two MO patients were grouped according to the absence (healthy: DM - DL -) or presence of comorbidities (dyslipidemic: DM - DL +; or dyslipidemic with type 2 diabetes: DM + DL +) before and one year after gastric bypass.
  
  
  RESULTS
  The livers of healthy, DL and DM patients contained more lipids (9.8, 9.5 and 13.7 times, respectively) than those of control subjects. The genes implicated in liver lipid uptake, including HL, LPL, VLDLr, and FAT/CD36, showed increased expression compared with the controls. The expression of genes involved in lipid-related processes outside of the liver, such as apoB, PPARα and PGC1α, CYP7a1 and HMGCR, was reduced in these patients compared with the controls. PAI1 and TNFα gene expression in the diabetic livers was increased compared with the other obese groups and control group. Increased steatosis and fibrosis were also noted in the MO individuals.
  
  
  CONCLUSIONS
  Hepatic lipid parameters in MO patients change based on their comorbidities. The gene expression and lipid levels after bariatric surgery were less prominent in the diabetic patients. Lipid receptor overexpression could enable the liver to capture circulating lipids, thus favouring the steatosis typically observed in diabetic and dyslipidaemic MO individuals.
authors.affiliation: Biochemistry and Molecular Biology Department, Biology Faculty, Barcelona University, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Pardina
authors.affiliation: Biochemistry Department, Hospital Universitari Vall D'Hebron, Universitat Autònoma de Barcelona, Spain.
authors.forename: Roser
authors.initials: R
authors.lastname: Ferrer
authors.affiliation: Biochemistry and Molecular Biology Department, Biology Faculty, Barcelona University, Spain.
authors.forename: Joana
authors.initials: J
authors.lastname: Rossell
authors.affiliation: Surgery Unit, Arnau de Vilanova University Hospital (UdL), Spain.
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Baena-Fustegueras
authors.affiliation: Endocrinology and Nutrition Department, Arnau de Vilanova University Hospital (UdL), Diabetes and Metabolism Research Unit (VHIR, UAB), CIBER de Diabetes y Enfermedades Metabólicas (CIBERDEM) del Instituto de Salud Carlos III, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Lecube
authors.affiliation: Endocrinology Surgery Unit, Hospital Universitari Vall D'Hebron, Universitat Autònoma de Barcelona, Spain.
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Fort
authors.affiliation: Endocrinology Surgery Unit, Hospital Universitari Vall D'Hebron, Universitat Autònoma de Barcelona, Spain.
authors.forename: Enric
authors.initials: E
authors.lastname: Caubet
authors.affiliation: Endocrinology Surgery Unit, Hospital Universitari Vall D'Hebron, Universitat Autònoma de Barcelona, Spain.
authors.forename: Óscar
authors.initials: Ó
authors.lastname: González
authors.affiliation: Endocrinology Surgery Unit, Hospital Universitari Vall D'Hebron, Universitat Autònoma de Barcelona, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Vilallonga
authors.affiliation: CIBER de Enfermedades Hepáticas y Digestivas (CIBEREHD) del Instituto de Salud Carlos III (ISCIII), Hospital Universitari Vall D'Hebron, Universitat Autònoma de Barcelona, Spain.
authors.forename: Víctor
authors.initials: V
authors.lastname: Vargas
authors.affiliation: Endocrinology Surgery Unit, Hospital Universitari Vall D'Hebron, Universitat Autònoma de Barcelona, Spain.
authors.forename: José María
authors.initials: JM
authors.lastname: Balibrea
authors.affiliation: Biochemistry and Molecular Biology Department, Biology Faculty, Barcelona University, Spain.
authors.forename: Julia
authors.initials: J
authors.lastname: Peinado-Onsurbe
keywords: ALT, Alanine transaminase; AST, Aspartate transaminase; ATGL, Adipose Tissue Glycerol Lipase; ApoA1, Apolipoprotein A1; BMI, Body Mass Index; CPT1a, Carnitine Palmitoyltransferase 1a; CRP, C-reactive protein; CYP7a1, Cholesterol 7 Alpha-Hydroxylase; DL, Dyslipidaemia; DM, Type 2 diabetes mellitus; DM + DL +,  Obese patients with type 2 diabetes and dyslipidaemia; DM − DL +,  Dyslipidemic obese patients; DM − DL −, “Healthy” obese patients, or patients without type 2 diabetes or dyslipidaemia; Diabetes; FAT/CD36, Fatty Acid Translocase or Cluster of Differentiation 36; GGT, gamma-glutaryl transferase; HL, Hepatic lipase; HMGCR, 3-Hydroxy-3-Methylglutaryl-CoA Reductase; HOMA-IR, Homeostasis Model Assessment of Insulin Resistance; HSL, Hormone-sensitive lipase; HTA, Hypertension; IL6, Interleukin-6; IR, Insulin resistance; KBs, Ketone bodies; LDLr, Low-Density Lipoprotein receptor; Lipases; Lipids; Liver; MO, Morbidly obese; NAFLD; NAFLD, Non-alcoholic fatty liver disease; NASH, Non-alcoholic liver steatohepatitis; NEFA, Non-esterified fatty acid; PAI1, Plasminogen Activator Inhibitor of Type 1; PLs, Phospholipids; PPARα, Peroxisome Proliferator-Activated Receptor alpha; PPARα, Peroxisome Proliferator-Activated Receptor gamma Coactivator 1-alpha; QMs, Chylomicrons; RYGBP, Roux-en-Y gastric bypass; SAT, Subcutaneous adipose tissue; SCARB1, Scavenger Receptor Class B, Member 1; Steatosis; TAGs, Triacylglycerides; TC, Total cholesterol; TNFα, Tumour Necrosis Factor-alpha; UCP2, Uncoupling Protein 2; VAT, Visceral adipose tissue; VLDLr, Very-Low-Density Lipoprotein receptor; apoB, Apolipoprotein B; cHDL, High-Density Lipoprotein Cholesterol; cLDL, Low-Density Lipoprotein Cholesterol; eNOS3, Endothelial Nitric Oxide Synthase 3; iNOS2, Inducible Nitric Oxide Synthase 2