Visceral adipose tissue-derived serine protease inhibitor

A unique insulin-sensitizing adipocytokine in obesity

Kazuyuki Hida, Jun Wada, Jun Eguchi, Hong Zhang, Masako Baba, Aya Seida, Izumi Hashimoto, Tatsuo Okada, Akihiro Yasuhara, Atsuko Nakatsuka, Kenichi Shikata, Shinji Hourai, Junichiro Futami, Eijiro Watanabe, Yasushi Matsuki, Ryuji Hiramatsu, Shigeru Akagi, Hirofumi Makino, Yashpal S. Kanwar

Research output: Contribution to journalArticle

476 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)10610-10615
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number30
DOIs
Publication statusPublished - Jul 26 2005

Fingerprint

Serine Proteinase Inhibitors
Adipokines
Intra-Abdominal Fat
Serpins
Obesity
White Adipose Tissue
Insulin
Inbred OLETF Rats
pioglitazone
Sucrose
Insulin Resistance
Serum
Fats
Body Weight
Resistin
Glucose
Inbred ICR Mouse
Facilitative Glucose Transport Proteins
Abdominal Obesity
Adiponectin

Keywords

  • Diabetes
  • Insulin resistance
  • Mesenteric
  • Metabolic syndrome
  • White adipose tissue

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Visceral adipose tissue-derived serine protease inhibitor : A unique insulin-sensitizing adipocytokine in obesity. / Hida, Kazuyuki; Wada, Jun; Eguchi, Jun; Zhang, Hong; Baba, Masako; Seida, Aya; Hashimoto, Izumi; Okada, Tatsuo; Yasuhara, Akihiro; Nakatsuka, Atsuko; Shikata, Kenichi; Hourai, Shinji; Futami, Junichiro; Watanabe, Eijiro; Matsuki, Yasushi; Hiramatsu, Ryuji; Akagi, Shigeru; Makino, Hirofumi; Kanwar, Yashpal S.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 30, 26.07.2005, p. 10610-10615.

Research output: Contribution to journalArticle

Hida, Kazuyuki ; Wada, Jun ; Eguchi, Jun ; Zhang, Hong ; Baba, Masako ; Seida, Aya ; Hashimoto, Izumi ; Okada, Tatsuo ; Yasuhara, Akihiro ; Nakatsuka, Atsuko ; Shikata, Kenichi ; Hourai, Shinji ; Futami, Junichiro ; Watanabe, Eijiro ; Matsuki, Yasushi ; Hiramatsu, Ryuji ; Akagi, Shigeru ; Makino, Hirofumi ; Kanwar, Yashpal S. / Visceral adipose tissue-derived serine protease inhibitor : A unique insulin-sensitizing adipocytokine in obesity. In: Proceedings of the National Academy of Sciences of the United States of America. 2005 ; Vol. 102, No. 30. pp. 10610-10615.
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