PPARγ mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance

被引：1147

作者：

Kubota, N

Terauchi, Y

Miki, H

Tamemoto, H

Yamauchi, T

Komeda, K

Satoh, S

Nakano, R

Ishii, C

Sugiyama, T

Eto, K

Tsubamoto, Y

Okuno, A

Murakami, K

Sekihara, H

Hasegawa, G

Naito, M

Toyoshima, Y

Tanaka, S

Shiota, K

Kitamura, T

Fujita, T

Ezaki, O

Aizawa, S

Nagai, R

Tobe, K

Kimura, S

Kadowaki, T ^{[1
]}

机构：

[1] Univ Tokyo, Grad Sch Vet Med Sci Anim Resource Sci, Dept Metab Dis, Tokyo 1138655, Japan

[2] Univ Tokyo, Grad Sch Vet Med Sci Anim Resource Sci, Dept Cardiovasc Dis, Tokyo 1138655, Japan

[3] Univ Tokyo, Grad Sch Med, Dept Nephrol & Endocrinol, Tokyo 1138655, Japan

[4] Gunma Univ, Inst Mol & Cellular Regulat, Dept Mol Med, Gunma 3718512, Japan

[5] Tokyo Med Univ, Anim Res Ctr, Div Lab Anim Sci, Tokyo 1608402, Japan

[6] Saitama Med Sch, Dept Internal Med 4, Moroyama, Saitama 3500495, Japan

[7] Niigata Univ, Sch Med, Dept Pathol 2, Niigata 9518510, Japan

[8] Natl Inst Hlth & Nutr, Div Clin Nutr, Tokyo 1628636, Japan

[9] Kumamoto Univ, Sch Med, Inst Mol Embryol & Genet, Dept Morphogenesis, Kumamoto 8620976, Japan

[10] Yokohama City Univ, Dept Internal Med 3, Yokohama, Kanagawa 2360004, Japan

[11] Univ Tokyo, Inst Med Sci, Dept Hematopoiet Factors, Minato Ku, Tokyo 1088639, Japan

来源：

MOLECULAR CELL | 1999年 / 4卷 / 04期

关键词：

D O I：

10.1016/S1097-2765(00)80210-5

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Agonist-induced activation of peroxisome proliferator-activated receptor gamma (PPAR gamma) is known to cause adipocyte differentiation and insulin sensitivity. The biological role of PPAR gamma was investigated by gene targeting. Homozygous PPAR gamma-deficient embryos died at 10.5-11.5 dpc due to placental dysfunction. Quite unexpectedly, heterozygous PPAR gamma-deficient mice were protected from the development of insulin resistance due to adipocyte hypertrophy under a high-fat diet. These phenotypes were abrogated by PPAR gamma agonist treatment. Heterozygous PPAR gamma-deficient mice showed overexpression and hypersecretion of leptin despite the smaller size of adipocytes and decreased fat mass, which may explain these phenotypes at least in part. This study reveals a hitherto unpredicted role for PPAR gamma in high-fat diet-induced obesity due to adipocyte hypertrophy and insulin resistance, which requires both alleles of PPAR gamma.

引用

页码：597 / 609

页数：13

共 24 条

[1] A Pro12Ala substitution in PPARγ2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity [J].