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

J Diabetes Res. 2018 Feb 25:2018:6823193. doi: 10.1155/2018/6823193. eCollection 2018.

Abstract

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.

MeSH terms

  • Animals
  • Atherosclerosis / etiology
  • Atherosclerosis / metabolism*
  • Atherosclerosis / pathology
  • Body Composition / physiology
  • Cholesterol, HDL / metabolism
  • Cholesterol, LDL / metabolism
  • Diet, High-Fat / adverse effects*
  • Female
  • Hypercholesterolemia / etiology
  • Hypercholesterolemia / metabolism*
  • Hypercholesterolemia / pathology
  • Insulin Resistance / physiology*
  • Intra-Abdominal Fat / metabolism
  • Metabolic Syndrome / etiology
  • Metabolic Syndrome / metabolism*
  • Metabolic Syndrome / pathology
  • Obesity, Abdominal / etiology
  • Obesity, Abdominal / metabolism*
  • Obesity, Abdominal / pathology
  • Subcutaneous Fat / metabolism
  • Swine
  • Swine, Miniature
  • Triglycerides / metabolism

Substances

  • Cholesterol, HDL
  • Cholesterol, LDL
  • Triglycerides