Kazuyuki Hida1, Jun Wada1, Jun Eguchi1, Hong Zhang1, Masako Baba1, Aya Seida1, Izumi Hashimoto1, Tatsuo Okada1, Akihiro Yasuhara1, Atsuko Nakatsuka1, Kenichi Shikata1, Shinji Hourai1, Junichiro Futami1, E. Watanabe1, Yasushi Matsuki1, Ryuji Hiramatsu1, Shigeru Akagi1, Hirofumi Makino1, Yashpal S. Kanwar1
1Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan; Department of Internal Medicine, Peking University Institute of Nephrology, Beijing 100034, P.R. China; Environmental Health Science Laboratory, Sumitomo Chemical Company, Osaka 554-8558, Japan; Department of Bioscience and Biotechnology, Okayama University Faculty of Engineering, Okayama 700-8530, Japan; Sumitomo Pharmaceuticals, Takarazuka 655-8555, Japan; and...
Tóm tắt
There is a rapid global rise in obesity, and the link between obesity and diabetes remains somewhat obscure. We identified an adipocytokine, designated as visceral adipose tissue-derived serpin (vaspin), which is a member of serine protease inhibitor family. Vaspin cDNA was isolated by from visceral white adipose tissues (WATs) of Otsuka Long-Evans Tokushima fatty (OLETF) rat, an animal model of abdominal obesity with type 2 diabetes. Rat, mouse, and human vaspins are made up of 392, 394, and 395 amino acids, respectively; exhibit ≈40% homology with α
1
-antitrypsin; and are related to serine protease inhibitor family. Vaspin was barely detectable in rats at 6 wk and was highly expressed in adipocytes of visceral WATs at 30 wk, the age when obesity, body weight, and insulin levels peak in OLETF rats. The tissue expression of vaspin and its serum levels decrease with worsening of diabetes and body weight loss at 50 wk. The expression and serum levels were normalized with the treatment of insulin or insulin-sensitizing agent, pioglitazone, in OLETF rats. Administration of vaspin to obese CRL:CD-1 (ICR) (ICR) mice fed with high-fat high-sucrose chow improved glucose tolerance and insulin sensitivity reflected by normalized serum glucose levels. It also led to the reversal of altered expression of genes relevant to insulin resistance, e.g., leptin, resistin, TNFα, glucose transporter-4, and adiponectin. In DNA chip analyses, vaspin treatment resulted in the reversal of expression in ≈50% of the high-fat high-sucrose-induced genes in WATs. These findings indicate that vaspin exerts an insulin-sensitizing effect targeted toward WATs in states of obesity.
