M. Gharedaghi1, M. Najibi1, S. Morrison1, K. Economopoulos1, T. Phupitakphol1, S. K. Hyoju1, A. Osmani1, S. R. Hamarneh1, R. A. Hodin1 1Massachusetts General Hospital,Department Of Surgery,Boston, MA, USA
Introduction: Intestinal alkaline phosphatase (IAP) is a brush border enzyme that plays a key role in the development of obesity and the metabolic syndrome (MetS). IAP-knockout (IAP-KO) mice are more susceptible to high fat diet (HFD)-induced MetS and oral supplementation with IAP has been shown to prevent the MetS in WT mice. The precise mechanism by which IAP works to prevent the MetS is not known. We therefore sought to compare the expression of metabolism-related genes between wild type (WT) and IAP-KO mice fed regular chow diet (CD) vs. HFD.
Methods: Six to eight week old IAP-KO and WT mice were fed with either CD or HFD for 23 weeks. The weight of the mice was registered weekly. Serum, liver and pancreatic tissue was harvested after sacrifice. Serum insulin levels were measured with enzyme linked immunosorbent assay. Expression of key metabolic genes in the liver and pancreatic tissues was determined by quantitative real time PCR. Data were expressed as mean ± standard error of mean (S.E.M.) and analysis of variance (ANOVA) and Tukey’s post hoc test was used to analyze the differences. P values less than 0.05 were considered as statistically significant.
Results: The percentage of weight gain was significantly higher in the HFD-fed IAP-KO mice in comparison to the CD- or HFD-fed WT mice (P = 0.041 and P= 0.047, respectively; Figure 1A). Although serum insulin levels trended upward in the HFD-fed IAP-KO mice, the analysis failed to reach statistical significance (ANOVA: P = 0.135; Figure 1B). The hepatic expression of lipoprotein lipase (LPL), peroxisome proliferator-activated receptor-γ (PPAR-γ) and acyl co-A dehydrogenase (ACAD) was significantly decreased in HFD-fed KO mice (Figures 1C, 1D and 1E). Interestingly, the decrease in hepatic expression of LPL was limited to IAP-KO mice and was not seen in HFD-fed WT mice (Figure 1C). Pancreatic expression of the adenosine triphosphate-sensitive inward rectifying potassium channel (kcnj11) was increased in HFD-fed IAP-KO mice suggesting alterations in the insulin secretion pathways (Figure 1F).
Conclusion: IAP has a significant effect on the expression of the genes which are involved in fat degradation and insulin secretion. Based on the LPL decrease in the IAP-KO but not the HFD-fed mice, it appears that IAP may prevent the metabolic syndrome through a mechanism that is distinct from dietary fat intake.
