Visceral adipose tissue-derived serine protease inhibitor: a unique insulin-sensitizing adipocytokine in obesity.
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 approximately 40% homology with alpha1-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, TNFalpha, glucose transporter-4, and adiponectin. In DNA chip analyses, vaspin treatment resulted in the reversal of expression in approximately 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.
Hida
Kazuyuki
K
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan.
Wada
Jun
J
Eguchi
Jun
J
Zhang
Hong
H
Baba
Masako
M
Seida
Aya
A
Hashimoto
Izumi
I
Okada
Tatsuo
T
Yasuhara
Akihiro
A
Nakatsuka
Atsuko
A
Shikata
Kenichi
K
Hourai
Shinji
S
Futami
Junichiro
J
Watanabe
Eijiro
E
Matsuki
Yasushi
Y
Hiramatsu
Ryuji
R
Akagi
Shigeru
S
Makino
Hirofumi
H
Kanwar
Yashpal S
YS
D017667:Adipocytes / Q000378:metabolism*; D000367:Age Factors; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001786:Blood Glucose; D015152:Blotting, Northern; D001835:Body Weight; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D000077205:Pioglitazone; D051381:Rats; D020334:Rats, Inbred OLETF; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D015843:Serpins / Q000235:genetics* / Q000378:metabolism; D045162:Thiazolidinediones
D001786:Blood Glucose; D007328:Insulin; C506516:Serpina12 protein, rat; D015843:Serpins; D045162:Thiazolidinediones; D000077205:Pioglitazone