Intestinal alkaline phosphatase prevents metabolic syndrome in mice.

Kanakaraju Kaliannan, Sulaiman R Hamarneh, Konstantinos P Economopoulos, Sayeda Nasrin Alam, Omeed Moaven, Palak Patel, Nondita S Malo, Madhury Ray, Seyed M Abtahi, Nur Muhammad, Atri Raychowdhury, Abeba Teshager, Mussa M Rafat Mohamed, Angela K Moss, Rizwan Ahmed, Shahrad Hakimian, Sonoko Narisawa, José Luis Millán, Elizabeth Hohmann, H Shaw Warren, Atul K Bhan, Madhu S Malo, Richard A Hodin

Index: Proc. Natl. Acad. Sci. U. S. A. 110(17) , 7003-8, (2013)

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Abstract

Metabolic syndrome comprises a cluster of related disorders that includes obesity, glucose intolerance, insulin resistance, dyslipidemia, and fatty liver. Recently, gut-derived chronic endotoxemia has been identified as a primary mediator for triggering the low-grade inflammation responsible for the development of metabolic syndrome. In the present study we examined the role of the small intestinal brush-border enzyme, intestinal alkaline phosphatase (IAP), in preventing a high-fat-diet-induced metabolic syndrome in mice. We found that both endogenous and orally supplemented IAP inhibits absorption of endotoxin (lipopolysaccharides) that occurs with dietary fat, and oral IAP supplementation prevents as well as reverses metabolic syndrome. Furthermore, IAP supplementation improves the lipid profile in mice fed a standard, low-fat chow diet. These results point to a potentially unique therapy against metabolic syndrome in at-risk humans.