title: Knockout of the l-pgds gene aggravates obesity and atherosclerosis in mice.
abstract: This study was designed to determine whether lipocalin type-prostaglandin D synthase (l-pgds) deficiency contributes to atherogenesis using gene knockout (KO) mice. A high-fat diet was given to 8-week-old C57BL/6 (wild type; WT), l-pgds KO (LKO), apolipoprotein E (apo E) KO (AKO) and l-pgds/apo E double KO (DKO) mice. The l-pgds deficient mice showed significantly increased body weight, which was accompanied by increased size of subcutaneous and visceral fat tissues. Fat deposition in the aortic wall induced by the high-fat diet was significantly increased in LKO mice compared with WT mice, although there was no significant difference between AKO and DKO mice. In LKO mice, atherosclerotic plaque in the aortic root was also increased and, furthermore, macrophage cellularity and the expression of pro-inflammatory cytokines such as interleukin-1beta and monocyte chemoattractant protein-1 were significant increased. In conclusion, l-pgds deficiency induces obesity and facilitates atherosclerosis, probably through the regulation of inflammatory responses.
authors.affiliation: Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Tanaka
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Miwa
authors.forename: Kin
authors.initials: K
authors.lastname: Mou
authors.forename: Morimasa
authors.initials: M
authors.lastname: Tomikawa
authors.forename: Naomi
authors.initials: N
authors.lastname: Eguchi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Urade
authors.forename: Fumi
authors.initials: F
authors.lastname: Takahashi-Yanaga
authors.forename: Sachio
authors.initials: S
authors.lastname: Morimoto
authors.forename: Norio
authors.initials: N
authors.lastname: Wake
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sasaguri
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics* / Q000473:pathology; D018932:Chemokine CCL2 / Q000096:biosynthesis; D005223:Fats / Q000378:metabolism; D055786:Gene Knockout Techniques; D007249:Inflammation / Q000235:genetics; D053583:Interleukin-1beta / Q000096:biosynthesis; D019746:Intramolecular Oxidoreductases / Q000235:genetics*; D054834:Lipocalins / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics* / Q000473:pathology; D015430:Weight Gain / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; D018932:Chemokine CCL2; D005223:Fats; D053583:Interleukin-1beta; D054834:Lipocalins; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase