Overexpression of adiponectin targeted to adipose tissue in transgenic mice: impaired adipocyte differentiation.
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 pre- adipocyte 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.
Bauche
Isabelle B
IB
Unité d'Endocrinologie et Métabolisme, University of Louvain/Endocrinology 5530, Avenue Hippocrate, 55, B-1200 Brussels, Belgium.
El Mkadem
Samira Ait
SA
Pottier
Anne-Marie
AM
Senou
Maximin
M
Many
Marie-Christine
MC
Rezsohazy
René
R
Penicaud
Luc
L
Maeda
Norikazu
N
Funahashi
Tohru
T
Brichard
Sonia M
SM
D017667:Adipocytes / Q000166:cytology*; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D004734:Energy Metabolism / Q000235:genetics; D050556:Fatty Acid-Binding Proteins / Q000235:genetics; D005260:Female; D005947:Glucose / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009928:Organ Specificity
D052242:Adiponectin; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D005947:Glucose