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. 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.

Low levels of haptoglobin and putative amino acid sequence in Taiwanese Lanyu miniature pigs.

Porcine haptoglobin (Hp) is an acute phase protein. Its plasma level increases significantly during inflammation and infection. One of the main functions of Hp is to bind free hemoglobin (Hb) and inhibit its oxidative activity. In the present report, we studied the Hp phenotype of Taiwanese Lanyu miniature pigs (TLY minipigs; n=43) and found their Hp structure to be a homodimer (beta-alpha-alpha-beta) similar to human Hp 1-1. Interestingly, Western blot and high performance liquid chromatographic (HPLC) analysis showed that 25% of the TLY minipigs possessed low or no plasma Hp level (<0.05 mg/ml). The Hp cDNA of these TLY minipigs was then cloned, and the translated amino acid sequence was analyzed. No sequences were found to be deficient; they showed a 99.7% identity with domestic pigs (NP_999165). The mean overall Hp level of the TLY minipigs (0.21 +/- 0.25 mg/ml; n=43) determined by enzyme-linked immunosorbent assay (ELISA) was markedly lower than that of domestic pigs (0.78 +/- 0.45 mg/ml; p<0.001), while 25% of the TLY minipigs had an Hp level that was extremely low (<0.05 mg/ml). In addition, the initial recovery rate (first 40 min) in the circulation of infused fluorescein isothiocyanate (FITC)-Hb was significantly higher in the TLY minipigs with extremely low Hp levels than those with high levels. This data suggests that the low concentration of Hp-Hb complex is responsible for the higher recovery rate of Hb in the circulation. TLY minipigs have been used as an experimental model for cardiovascular diseases; whether they can be used as a model for inflammatory diseases, with Hp as a marker, remains a topic of interest. However, since the Hp level varies significantly among individual TLY minipigs, it is necessary to prescreen the Hp levels of the animals to minimize variation in the experimental baseline. The present study may provide a reference value for future use of the TLY minipig as an animal model for inflammation-associated diseases.