Knockout of the l-pgds gene aggravates obesity and atherosclerosis in mice.
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.
Tanaka
Reiko
R
Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
Miwa
Yoshikazu
Y
Mou
Kin
K
Tomikawa
Morimasa
M
Eguchi
Naomi
N
Urade
Yoshihiro
Y
Takahashi-Yanaga
Fumi
F
Morimoto
Sachio
S
Wake
Norio
N
Sasaguri
Toshiyuki
T
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
D001057:Apolipoproteins E; D018932:Chemokine CCL2; D005223:Fats; D053583:Interleukin-1beta; D054834:Lipocalins; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase