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


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.


CONCLUSIONS
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.
Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan.
Sin-Jin
SJ
Li
Chia-Hsin
CH
Liu
Chei-Wei
CW
Chang
Hsien-Pin
HP
Chu
Kuen-Jaw
KJ
Chen
Harry J
HJ
Mersmann
Shih-Torng
ST
Ding
Chun-Han
CH
Chu
Ching-Yi
CY
Chen
D055372:AMP-Activated Protein Kinases / Q000502:physiology*; D000818:Animals; D066273:Diet, Western / Q000009:adverse effects*; D004195:Disease Models, Animal; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006937:Hypercholesterolemia / Q000209:etiology; D008099:Liver / Q000502:physiology; D008297:Male; D024821:Metabolic Syndrome / Q000209:etiology*; D009765:Obesity / Q000209:etiology; D011897:Random Allocation; D056564:Sirtuin 1 / Q000502:physiology*; D013552:Swine; D013556:Swine, Miniature
D051858:Forkhead Transcription Factors; D055372:AMP-Activated Protein Kinases; D056564:Sirtuin 1
AMPK; Lanyu miniature pig; Lee-Sung miniature pig; SIRT1; metabolic syndrome; metabolically healthy obesity