TY - JOUR
T1 - Visceral adipose tissue-derived serine protease inhibitor
T2 - A unique insulin-sensitizing adipocytokine in obesity
AU - Hida, Kazuyuki
AU - Wada, Jun
AU - Eguchi, Jun
AU - Zhang, Hong
AU - Baba, Masako
AU - Seida, Aya
AU - Hashimoto, Izumi
AU - Okada, Tatsuo
AU - Yasuhara, Akihiro
AU - Nakatsuka, Atsuko
AU - Shikata, Kenichi
AU - Hourai, Shinji
AU - Futami, Junichiro
AU - Watanabe, Eijiro
AU - Matsuki, Yasushi
AU - Hiramatsu, Ryuji
AU - Akagi, Shigeru
AU - Makino, Hirofumi
AU - Kanwar, Yashpal S.
PY - 2005/7/26
Y1 - 2005/7/26
N2 - 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 α1-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.
AB - 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 α1-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.
KW - Diabetes
KW - Insulin resistance
KW - Mesenteric
KW - Metabolic syndrome
KW - White adipose tissue
UR - http://www.scopus.com/inward/record.url?scp=23044473651&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=23044473651&partnerID=8YFLogxK
U2 - 10.1073/pnas.0504703102
DO - 10.1073/pnas.0504703102
M3 - Article
C2 - 16030142
AN - SCOPUS:23044473651
SN - 0027-8424
VL - 102
SP - 10610
EP - 10615
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 30
ER -
