TY - JOUR
T1 - Diet-Induced Abdominal Obesity, Metabolic Changes, and Atherosclerosis in Hypercholesterolemic Minipigs
AU - Al-Mashhadi, Ahmed Ludvigsen
AU - Poulsen, Christian Bo
AU - von Wachenfeldt, Karin
AU - Robertson, Anna-Karin
AU - Bentzon, Jacob Fog
AU - Nielsen, Lars Bo
AU - Thygesen, Jesper
AU - Tolbod, Lars Poulsen
AU - Larsen, Jens Rolighed
AU - Moestrup, Søren Kragh
AU - Frendéus, Björn
AU - Mortensen, Brynjulf
AU - Drouet, Ludovic
AU - Al-Mashhadi, Rozh H
AU - Falk, Erling
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - Animals
KW - Atherosclerosis/etiology
KW - Body Composition/physiology
KW - Cholesterol, HDL/metabolism
KW - Cholesterol, LDL/metabolism
KW - Diet, High-Fat/adverse effects
KW - Female
KW - Hypercholesterolemia/etiology
KW - Insulin Resistance/physiology
KW - Intra-Abdominal Fat/metabolism
KW - Metabolic Syndrome/etiology
KW - Obesity, Abdominal/etiology
KW - Subcutaneous Fat/metabolism
KW - Swine
KW - Swine, Miniature
KW - Triglycerides/metabolism
U2 - 10.1155/2018/6823193
DO - 10.1155/2018/6823193
M3 - Journal article
C2 - 29682581
SN - 2314-6745
VL - 2018
SP - 6823193
JO - Journal of Diabetes Research
JF - Journal of Diabetes Research
ER -