Intestinal alkaline phosphatase prevents metabolic syndrome in mice

Proc Natl Acad Sci U S A. 2013 Apr 23;110(17):7003-8. doi: 10.1073/pnas.1220180110. Epub 2013 Apr 8.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorption / drug effects
  • Administration, Oral
  • Alkaline Phosphatase / administration & dosage
  • Alkaline Phosphatase / genetics
  • Alkaline Phosphatase / metabolism*
  • Alkaline Phosphatase / pharmacology*
  • Animals
  • Azo Compounds
  • Cell Line
  • DNA Primers / genetics
  • Lipopolysaccharides
  • Liver / metabolism
  • Metabolic Syndrome / drug therapy*
  • Metabolic Syndrome / etiology
  • Metabolic Syndrome / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microvilli / metabolism
  • Real-Time Polymerase Chain Reaction
  • Triglycerides / metabolism


  • Azo Compounds
  • DNA Primers
  • Lipopolysaccharides
  • Triglycerides
  • Akp3 protein, mouse
  • Alkaline Phosphatase
  • oil red O