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Pronounced adipogenesis and increased insulin sensitivity caused by overproduction of prostaglandin D 2 in vivo
Author(s) -
Fujitani Yasushi,
Aritake Kosuke,
Kanaoka Yoshihide,
Goto Tsuyoshi,
Takahashi Nobuyuki,
Fujimori Ko,
Kawada Teruo
Publication year - 2010
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2010.07565.x
Subject(s) - medicine , endocrinology , adipogenesis , adipose tissue , insulin , white adipose tissue , in vivo , chemistry , insulin resistance , glucose homeostasis , insulin tolerance test , leptin , triglyceride , biology , cholesterol , obesity , insulin sensitivity , microbiology and biotechnology
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 γ, 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.