Diet-Induced Abdominal Obesity, Metabolic Changes, and Atherosclerosis in Hypercholesterolemic Minipigs

Background. Obesity and metabolic syndrome (MetS) are major risk factors for atherosclerotic diseases; however, a causal link remains elusive. Animal models resembling human MetS and its complications, while important, are scarce. We aimed at developing a porcine model of human MetS. Methods. Forty...

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Main Authors: Ahmed Ludvigsen Al-Mashhadi, Christian Bo Poulsen, Karin von Wachenfeldt, Anna-Karin Robertson, Jacob Fog Bentzon, Lars Bo Nielsen, Jesper Thygesen, Lars Poulsen Tolbod, Jens Rolighed Larsen, Søren Kragh Moestrup, Björn Frendéus, Brynjulf Mortensen, Ludovic Drouet, Rozh H. Al-Mashhadi, Erling Falk
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2018/6823193
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author Ahmed Ludvigsen Al-Mashhadi
Christian Bo Poulsen
Karin von Wachenfeldt
Anna-Karin Robertson
Jacob Fog Bentzon
Lars Bo Nielsen
Jesper Thygesen
Lars Poulsen Tolbod
Jens Rolighed Larsen
Søren Kragh Moestrup
Björn Frendéus
Brynjulf Mortensen
Ludovic Drouet
Rozh H. Al-Mashhadi
Erling Falk
author_facet Ahmed Ludvigsen Al-Mashhadi
Christian Bo Poulsen
Karin von Wachenfeldt
Anna-Karin Robertson
Jacob Fog Bentzon
Lars Bo Nielsen
Jesper Thygesen
Lars Poulsen Tolbod
Jens Rolighed Larsen
Søren Kragh Moestrup
Björn Frendéus
Brynjulf Mortensen
Ludovic Drouet
Rozh H. Al-Mashhadi
Erling Falk
author_sort Ahmed Ludvigsen Al-Mashhadi
collection DOAJ
description Background. Obesity and metabolic syndrome (MetS) are major risk factors for atherosclerotic diseases; however, a causal link remains elusive. Animal models resembling human MetS and its complications, while important, are scarce. We aimed at developing a porcine model of human MetS. Methods. Forty pigs with familial hypercholesterolemia were fed a high fat + fructose diet for 30 weeks. Metabolic assessments and subcutaneous fat biopsies were obtained at 18 and 30 weeks, and fat distribution was assessed by CT-scans. Postmortem, macrophage density, and phenotype in fat tissues were quantified along with atherosclerotic burden. Results. During the experiment, we observed a >4-fold in body weight, a significant but small increase in fasting glucose (4.1 mmol/L), insulin (3.1 mU/L), triglycerides (0.5 mmol/L), and HDL cholesterol (2.6 mmol/L). Subcutaneous fat correlated with insulin resistance, but intra-abdominal fat correlated inversely with insulin resistance and LDL cholesterol. More inflammatory macrophages were found in visceral versus subcutaneous fat, and inflammation decreased in subcutaneous fat over time. Conclusions. MetS based on human criteria was not achieved. Surprisingly, visceral fat seemed part of a healthier metabolic and inflammatory profile. These results differ from human findings, and further research is needed to understand the relationship between obesity and MetS in porcine models.
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spelling doaj-art-2c21b3e715324ff9bbb4daf88ef553992025-08-20T02:07:38ZengWileyJournal of Diabetes Research2314-67452314-67532018-01-01201810.1155/2018/68231936823193Diet-Induced Abdominal Obesity, Metabolic Changes, and Atherosclerosis in Hypercholesterolemic MinipigsAhmed Ludvigsen Al-Mashhadi0Christian Bo Poulsen1Karin von Wachenfeldt2Anna-Karin Robertson3Jacob Fog Bentzon4Lars Bo Nielsen5Jesper Thygesen6Lars Poulsen Tolbod7Jens Rolighed Larsen8Søren Kragh Moestrup9Björn Frendéus10Brynjulf Mortensen11Ludovic Drouet12Rozh H. Al-Mashhadi13Erling Falk14Department of Clinical Medicine, Aarhus University and Department of Cardiology, Aarhus University Hospital, Aarhus, DenmarkDepartment of Clinical Medicine, Aarhus University and Department of Cardiology, Aarhus University Hospital, Aarhus, DenmarkTruly Translational, Lund, SwedenBioInvent International AB, Lund, SwedenDepartment of Clinical Medicine, Aarhus University and Department of Cardiology, Aarhus University Hospital, Aarhus, DenmarkDepartment of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, DenmarkDepartment of Biomedical Engineering, Aarhus University Hospital, Aarhus, DenmarkDepartment of Nuclear Medicine and PET-Centre, Aarhus University Hospital, Aarhus, DenmarkDepartment of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Aarhus, DenmarkDepartment of Molecular Medicine, University of Southern Denmark, Odense, DenmarkBioInvent International AB, Lund, SwedenCenter for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, DenmarkInstitute of Vessels and Blood, Hospital Lariboisiere, Paris, FranceDepartment of Clinical Medicine, Aarhus University and Department of Cardiology, Aarhus University Hospital, Aarhus, DenmarkDepartment of Clinical Medicine, Aarhus University and Department of Cardiology, Aarhus University Hospital, Aarhus, DenmarkBackground. Obesity and metabolic syndrome (MetS) are major risk factors for atherosclerotic diseases; however, a causal link remains elusive. Animal models resembling human MetS and its complications, while important, are scarce. We aimed at developing a porcine model of human MetS. Methods. Forty pigs with familial hypercholesterolemia were fed a high fat + fructose diet for 30 weeks. Metabolic assessments and subcutaneous fat biopsies were obtained at 18 and 30 weeks, and fat distribution was assessed by CT-scans. Postmortem, macrophage density, and phenotype in fat tissues were quantified along with atherosclerotic burden. Results. During the experiment, we observed a >4-fold in body weight, a significant but small increase in fasting glucose (4.1 mmol/L), insulin (3.1 mU/L), triglycerides (0.5 mmol/L), and HDL cholesterol (2.6 mmol/L). Subcutaneous fat correlated with insulin resistance, but intra-abdominal fat correlated inversely with insulin resistance and LDL cholesterol. More inflammatory macrophages were found in visceral versus subcutaneous fat, and inflammation decreased in subcutaneous fat over time. Conclusions. MetS based on human criteria was not achieved. Surprisingly, visceral fat seemed part of a healthier metabolic and inflammatory profile. These results differ from human findings, and further research is needed to understand the relationship between obesity and MetS in porcine models.http://dx.doi.org/10.1155/2018/6823193
spellingShingle Ahmed Ludvigsen Al-Mashhadi
Christian Bo Poulsen
Karin von Wachenfeldt
Anna-Karin Robertson
Jacob Fog Bentzon
Lars Bo Nielsen
Jesper Thygesen
Lars Poulsen Tolbod
Jens Rolighed Larsen
Søren Kragh Moestrup
Björn Frendéus
Brynjulf Mortensen
Ludovic Drouet
Rozh H. Al-Mashhadi
Erling Falk
Diet-Induced Abdominal Obesity, Metabolic Changes, and Atherosclerosis in Hypercholesterolemic Minipigs
Journal of Diabetes Research
title Diet-Induced Abdominal Obesity, Metabolic Changes, and Atherosclerosis in Hypercholesterolemic Minipigs
title_full Diet-Induced Abdominal Obesity, Metabolic Changes, and Atherosclerosis in Hypercholesterolemic Minipigs
title_fullStr Diet-Induced Abdominal Obesity, Metabolic Changes, and Atherosclerosis in Hypercholesterolemic Minipigs
title_full_unstemmed Diet-Induced Abdominal Obesity, Metabolic Changes, and Atherosclerosis in Hypercholesterolemic Minipigs
title_short Diet-Induced Abdominal Obesity, Metabolic Changes, and Atherosclerosis in Hypercholesterolemic Minipigs
title_sort diet induced abdominal obesity metabolic changes and atherosclerosis in hypercholesterolemic minipigs
url http://dx.doi.org/10.1155/2018/6823193
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