Development of a dietary-induced metabolic syndrome model using miniature pigs involvement of AMPK and SIRT1

Eur J Clin Invest. 2015 Jan;45(1):70-80. doi: 10.1111/eci.12370. Epub 2014 Nov 26.

Abstract

Background: During the progression of the metabolic syndrome (MetS), cardiovascular diseases (CVD) appear clinically in many individuals and cause death. As a result, it is essential to set up an optimal animal model to study the mechanism of MetS leading to CVD. SIRT1 and AMPK are the master regulators of lipid and carbohydrate metabolism. The objective of this study was to establish a miniature pig model of Western diet-induced MetS and investigate the role of SIRT1/AMPK during MetS development.

Materials and methods: Five-month-old Lee-Sung (LS) and Lanyu (LY) minipigs were each randomly assigned to two groups: control diet (C) and Western diet (W), in a 6-month experimental period.

Results: Western diet caused obesity in both minipig models. Compared with the CLS pigs, WLS pigs exhibited hypercholesterolaemia. However, WLY pigs maintained a similar plasma lipid profile to the CLY pigs. Western diet caused a lower antioxidant capacity in the liver of both pig models. WLS pigs had higher triglyceride accumulation in the liver than CLS pigs, whereas WLY and CLY pigs had similar hepatic triglyceride accumulation. Compared with CLS pigs, WLS pigs had a lower hepatic SIRT1 expression, whereas WLY pigs had a higher expression of AMPK, FOXO1 and SIRT1 than CLY pigs.

Conclusion: Long-term feeding of the Western diet to Lee-Sung miniature pigs not only caused obesity but also induced MetS and fatty liver, whereas Western diet induced obesity in Lanyu pigs without metabolic dysfunctions. SIRT1/AMPK and their downstream pathways might be one of the possible regulators for pathological obesity in Lee-Sung pigs.

Keywords: AMPK; Lanyu miniature pig; Lee-Sung miniature pig; SIRT1; metabolic syndrome; metabolically healthy obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / physiology*
  • Animals
  • Diet, Western / adverse effects*
  • Disease Models, Animal
  • Female
  • Forkhead Transcription Factors / metabolism
  • Hypercholesterolemia / etiology
  • Liver / physiology
  • Male
  • Metabolic Syndrome / etiology*
  • Obesity / etiology
  • Random Allocation
  • Sirtuin 1 / physiology*
  • Swine
  • Swine, Miniature

Substances

  • Forkhead Transcription Factors
  • AMP-Activated Protein Kinases
  • Sirtuin 1