Pronounced adipogenesis and increased insulin sensitivity caused by overproduction of prostaglandin D2 in vivo.
Lipocalin-type prostaglandin (PG) D synthase is expressed in adipose tissues and involved in the regulation of glucose tolerance and atherosclerosis in type 2 diabetes. However, the physiological roles of PGD(2) in adipogenesis in vivo are not clear, as lipocalin-type prostaglandin D synthase can also act as a transporter for lipophilic molecules, such as retinoids. We generated transgenic (TG) mice overexpressing human hematopoietic PGDS (H-PGDS) and investigated the in vivo functions of PGD(2) in adipogenesis. PGD(2) production in white adipose tissue of H-PGDS TG mice was increased approximately seven-fold as compared with that in wild-type (WT) mice. With a high-fat diet, H-PGDS TG mice gained more body weight than WT mice. Serum leptin and insulin levels were increased in H-PGDS TG mice, and the triglyceride level was decreased by about 50% as compared with WT mice. Furthermore, in the white adipose tissue of H-PGDS TG mice, transcription levels of peroxisome proliferator-activated receptor gamma, fatty acid binding protein 4 and lipoprotein lipase were increased approximately two-fold to five-fold as compared with those of WT mice. Finally, H-PGDS TG mice showed clear hypoglycemia after insulin clamp. These results indicate that TG mice overexpressing H-PGDS abundantly produced PGD(2) in adipose tissues, resulting in pronounced adipogenesis and increased insulin sensitivity. The present study provides the first evidence that PGD(2) participates in the differentiation of adipocytes and in insulin sensitivity in vivo, and the H-PGDS TG mice could constitute a novel model mouse for diabetes studies.
Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Japan.
Yasushi
Y
Fujitani
Kosuke
K
Aritake
Yoshihide
Y
Kanaoka
Tsuyoshi
T
Goto
Nobuyuki
N
Takahashi
Ko
K
Fujimori
Teruo
T
Kawada
D017667:Adipocytes / Q000166:cytology; D050156:Adipogenesis / Q000187:drug effects* / Q000235:genetics; D000818:Animals; D001786:Blood Glucose; D001835:Body Weight; D002454:Cell Differentiation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental; D004041:Dietary Fats / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009765:Obesity; D015230:Prostaglandin D2 / Q000378:metabolism* / Q000494:pharmacology; D015854:Up-Regulation
D001786:Blood Glucose; D004041:Dietary Fats; D015230:Prostaglandin D2