title: Intestinal alkaline phosphatase prevents metabolic syndrome in mice.
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.
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Kanakaraju
authors.initials: K
authors.lastname: Kaliannan
authors.forename: Sulaiman R
authors.initials: SR
authors.lastname: Hamarneh
authors.forename: Konstantinos P
authors.initials: KP
authors.lastname: Economopoulos
authors.forename: Sayeda
authors.initials: S
authors.lastname: Nasrin Alam
authors.forename: Omeed
authors.initials: O
authors.lastname: Moaven
authors.forename: Palak
authors.initials: P
authors.lastname: Patel
authors.forename: Nondita S
authors.initials: NS
authors.lastname: Malo
authors.forename: Madhury
authors.initials: M
authors.lastname: Ray
authors.forename: Seyed M
authors.initials: SM
authors.lastname: Abtahi
authors.forename: Nur
authors.initials: N
authors.lastname: Muhammad
authors.forename: Atri
authors.initials: A
authors.lastname: Raychowdhury
authors.forename: Abeba
authors.initials: A
authors.lastname: Teshager
authors.forename: Mussa M Rafat
authors.initials: MM
authors.lastname: Mohamed
authors.forename: Angela K
authors.initials: AK
authors.lastname: Moss
authors.forename: Rizwan
authors.initials: R
authors.lastname: Ahmed
authors.forename: Shahrad
authors.initials: S
authors.lastname: Hakimian
authors.forename: Sonoko
authors.initials: S
authors.lastname: Narisawa
authors.forename: José Luis
authors.initials: JL
authors.lastname: Millán
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hohmann
authors.forename: H Shaw
authors.initials: HS
authors.lastname: Warren
authors.forename: Atul K
authors.initials: AK
authors.lastname: Bhan
authors.forename: Madhu S
authors.initials: MS
authors.lastname: Malo
authors.forename: Richard A
authors.initials: RA
authors.lastname: Hodin
mesh_terms: D000042:Absorption / Q000187:drug effects; D000284:Administration, Oral; D000469:Alkaline Phosphatase / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D001391:Azo Compounds; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D008070:Lipopolysaccharides; D008099:Liver / Q000378:metabolism; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008871:Microvilli / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014280:Triglycerides / Q000378:metabolism
chemical_list: D001391:Azo Compounds; D017931:DNA Primers; D008070:Lipopolysaccharides; D014280:Triglycerides; C520837:Akp3 protein, mouse; D000469:Alkaline Phosphatase; C011049:oil red O