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

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 -