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 L
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, B
AU - Drouet, J.-L.
AU - Al-Mashhadi, Rozh
AU - Falk, Erling
PY - 2018/2/25
Y1 - 2018/2/25
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
JO - Journal of Diabetes Research
JF - Journal of Diabetes Research
M1 - 6823193
ER -