title: High dietary fat-induced obesity in Wistar rats and type 2 diabetes in nonobese Goto-Kakizaki rats differentially affect retinol binding protein 4 expression and vitamin A metabolism.
abstract: Obesity is a major risk factor for type 2 diabetes, which is caused mainly by insulin resistance. Retinol binding protein 4 (RBP4) is the only specific transport protein for retinol in the serum. RBP4 level is increased in the diabetic state and high-fat condition, indicating that retinol metabolism may be affected under these conditions. However, the precise effect of diabetes and high fat-induced obesity on retinol metabolism is unknown. In this study, we examined differences in retinol metabolite levels in rat models of diet-induced obesity and type 2 diabetes (Goto-Kakizaki [GK] rat). Four-week-old male Wistar and GK rats were given either a control diet (AIN-93G) or a high-fat diet (HFD, 40% fat kJ). After 15 weeks of feeding, the RBP4 levels increased by 2-fold in the serum of GK rats but not HFD-fed rats. The hepatic retinol concentration of HFD-fed rats was approximately 50% that of the controls (P < .01). In contrast, the renal retinol concentrations of GK rats increased by 70% (P < .01). However, expression of RARβ in the kidney, which was induced in a retinoic acid-dependent manner, was downregulated by 90% (P < .01) in GK rats. In conclusion, diabetes and obesity affected retinol metabolism differently, and the effects were different in different peripheral tissues. The impact of HFD may be limited to the storage of hepatic vitamin A as retinyl palmitate. In particular, our data indicate that renal retinoic acid production might represent an important target for the treatment of type 2 diabetes mellitus.
authors.affiliation: Department of Applied Biology and Chemistry, Faculty of Applied Bioscience, Tokyo university of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Shirai
authors.affiliation: Department of Applied Biology and Chemistry, Faculty of Applied Bioscience, Tokyo university of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Shichi
authors.affiliation: Department of Applied Biology and Chemistry, Faculty of Applied Bioscience, Tokyo university of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Sato
authors.affiliation: Department of Nutrition, Junior College of Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, 156-8502, Tokyo, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Tanioka
authors.affiliation: Department of Nutrition, Junior College of Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, 156-8502, Tokyo, Japan.
authors.forename: Tadasu
authors.initials: T
authors.lastname: Furusho
authors.affiliation: Department of Nutritional Sciences, Faculty of Nutritional Sciences, The University of Morioka, 808 Sunagome, Takizawa, Iwate 020-0813, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Ota
authors.affiliation: Department of Applied Biology and Chemistry, Faculty of Applied Bioscience, Tokyo university of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan.
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Tadokoro
authors.affiliation: Department of Applied Biology and Chemistry, Faculty of Applied Bioscience, Tokyo university of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Applied Biology and Chemistry, Faculty of Applied Bioscience, Tokyo university of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Department of Applied Biology and Chemistry, Faculty of Applied Bioscience, Tokyo university of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan. Electronic address: yujiya@nodai.ac.jp.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yamamoto
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D059305:Diet, High-Fat / Q000009:adverse effects*; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects; D004224:Diterpenes; D015536:Down-Regulation; D007328:Insulin / Q000097:blood; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000097:blood / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D054839:Retinol-Binding Proteins, Plasma / Q000235:genetics / Q000378:metabolism*; D000084562:Retinyl Esters; D014801:Vitamin A / Q000031:analogs & derivatives / Q000097:blood* / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D004224:Diterpenes; D007328:Insulin; C532035:Rbp4 protein, rat; D018168:Receptors, Retinoic Acid; D054839:Retinol-Binding Proteins, Plasma; D000084562:Retinyl Esters; C082925:retinoic acid receptor beta; D014801:Vitamin A; C014794:retinol palmitate
keywords: Diabetes; GK rat; High-fat diet; RBP4; Vitamin A