Overexpression of adiponectin targeted to adipose tissue in transgenic mice: Impaired adipocyte differentiation

被引:103
作者
Bauche, Isabelle B.
El Mkadem, Samira Ait
Pottier, Anne-Marie
Senou, Maximin
Many, Marie-Christine
Rezsohazy, Rene
Penicaud, Luc
Maeda, Norikazu
Funahashi, Tohru
Brichard, Sonia M.
机构
[1] Univ Louvain, Unite Endocrinol & Metab, Fac Med, B-1200 Brussels, Belgium
[2] Univ Louvain, Expt Morphol Unit, Fac Med, B-1200 Brussels, Belgium
[3] Univ Louvain, Inst Sci Vie, Unit Vet Sci, B-1348 Louvain, Belgium
[4] CNRS, UMR 5018, F-31062 Toulouse, France
[5] Univ Toulouse 3, F-31062 Toulouse, France
[6] Osaka Univ, Grad Sch Med, Dept Internal Med & Mol Sci, Osaka 5600043, Japan
关键词
ACTIVATED PROTEIN-KINASE; FATTY-ACID OXIDATION; INSULIN-RESISTANCE; IN-VITRO; GLOBULAR DOMAIN; SKELETAL-MUSCLE; DEFICIENT MICE; OB/OB MICE; EXPRESSION; GLUCOSE;
D O I
10.1210/en.2006-0838
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Adiponectin (ApN) is an adipokine whose expression and plasma levels are inversely related to obesity and insulin-resistant states. Chronic repercussions of ApN treatment or overexpression on adiposity and body weight are still controversial. Here, we generated a transgenic (Tg) mouse model allowing persistent and moderate overexpression of native full-length ApN targeted to white adipose tissue. Adipose mass and adipocyte size of Tg mice were reduced despite preserved calorie intake. This reduction resulted from increased energy expenditure and up-regulation of uncoupling proteins, and from abrogation of the adipocyte differentiation program, as shown by the loss of a key lipogenic enzyme and of adipocyte markers. Adipose mass remodeling favors enhanced insulin sensitivity and improved lipid profile of Tg mice. Alteration of the adipocyte phenotype was likely to result from increased expression of the preadipocyte factor-1 and from down-regulation of the transcription factor, CCAAT/enhancer binding protein-alpha, which orchestrates adipocyte differentiation. We further found that recombinant ApN directly stimulated preadipocyte factor-1 mRNA and attenuated CCAAT/enhancer binding protein-alpha expression in cultured 3T3-F442A cells. Conversely, opposite changes in the expression of these genes were observed in white fat of ApN-deficient mice. Thus, besides enhanced energy expenditure, our work shows that impairment of adipocyte differentiation contributes to the anti-adiposity effect of ApN.
引用
收藏
页码:1539 / 1549
页数:11
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