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Pardina E, Ferrer R, Rossell J, et al. Diabetic and dyslipidaemic morbidly obese exhibit more liver alterations compared with healthy morbidly obese. BBA Clin. 2016;5:54-65doi: 10.1016/j.bbacli.2015.12.002.
Pardina, E., Ferrer, R., Rossell, J., Baena-Fustegueras, J. A., Lecube, A., Fort, J. M., Caubet, E., González, �. �., Vilallonga, R., Vargas, V., Balibrea, J. M., & Peinado-Onsurbe, J. (2016). Diabetic and dyslipidaemic morbidly obese exhibit more liver alterations compared with healthy morbidly obese. BBA clinical, 554-65. https://doi.org/10.1016/j.bbacli.2015.12.002
Pardina, Eva, et al. "Diabetic and dyslipidaemic morbidly obese exhibit more liver alterations compared with healthy morbidly obese." BBA clinical vol. 5 (2016): 54-65. doi: https://doi.org/10.1016/j.bbacli.2015.12.002
Pardina E, Ferrer R, Rossell J, Baena-Fustegueras JA, Lecube A, Fort JM, Caubet E, González Ó, Vilallonga R, Vargas V, Balibrea JM, Peinado-Onsurbe J. Diabetic and dyslipidaemic morbidly obese exhibit more liver alterations compared with healthy morbidly obese. BBA Clin. 2016 Jan 08;5:54-65. doi: 10.1016/j.bbacli.2015.12.002. eCollection 2016 Jun. PMID: 27051590; PMCID: PMC4802404.
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BBA Clin. 2016 Jan 08;5:54-65. doi: 10.1016/j.bbacli.2015.12.002. eCollection 2016 Jun.

Diabetic and dyslipidaemic morbidly obese exhibit more liver alterations compared with healthy morbidly obese.

BBA clinical

Eva Pardina, Roser Ferrer, Joana Rossell, Juan Antonio Baena-Fustegueras, Albert Lecube, Jose Manuel Fort, Enric Caubet, Óscar González, Ramón Vilallonga, Víctor Vargas, José María Balibrea, Julia Peinado-Onsurbe

Affiliations

  1. Biochemistry and Molecular Biology Department, Biology Faculty, Barcelona University, Spain.
  2. Biochemistry Department, Hospital Universitari Vall D'Hebron, Universitat Autònoma de Barcelona, Spain.
  3. Surgery Unit, Arnau de Vilanova University Hospital (UdL), Spain.
  4. 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.
  5. Endocrinology Surgery Unit, Hospital Universitari Vall D'Hebron, Universitat Autònoma de Barcelona, Spain.
  6. CIBER de Enfermedades Hepáticas y Digestivas (CIBEREHD) del Instituto de Salud Carlos III (ISCIII), Hospital Universitari Vall D'Hebron, Universitat Autònoma de Barcelona, Spain.

PMID: 27051590 PMCID: PMC4802404 DOI: 10.1016/j.bbacli.2015.12.002

Abstract

BACKGROUND & AIMS: 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.

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

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