Abstract

Negative regulators of white adipose tissue (WAT) expansion are poorly documented in vivo. Prostaglandin F(2α) (PGF(2α)) is a potent antiadipogenic factor in cultured preadipocytes, but evidence for its involvement in physiological context is lacking. We previously reported that Akr1b7, an aldo-keto reductase enriched in adipose stromal vascular fraction but absent from mature adipocytes, has antiadipogenic properties possibly supported by PGF(2α) synthase activity. To test whether lack of Akr1b7 could influence WAT homeostasis in vivo, we generated Akr1b7(-/-) mice in 129/Sv background. Akr1b7(-/-) mice displayed excessive basal adiposity resulting from adipocyte hyperplasia/hypertrophy and exhibited greater sensitivity to diet-induced obesity. Following adipose enlargement and irrespective of the diet, they developed liver steatosis and progressive insulin resistance. Akr1b7 loss was associated with decreased PGF(2α) WAT contents. Cloprostenol (PGF(2α) agonist) administration to Akr1b7(-/-) mice normalized WAT expansion by affecting both de novo adipocyte differentiation and size. Treatment of 3T3-L1 adipocytes and Akr1b7(-/-) mice with cloprostenol suggested that decreased adipocyte size resulted from inhibition of lipogenic gene expression. Hence, Akr1b7 is a major regulator of WAT development through at least two PGF(2α)-dependent mechanisms: inhibition of adipogenesis and lipogenesis. These findings provide molecular rationale to explore the status of aldo-keto reductases in dysregulations of adipose tissue homeostasis.

Links

Publisher Full Text

Authors

Volat FE, Pointud JC, Pastel E, Morio B, Sion B, Hamard G, Guichardant M, Colas R, Lefrançois-Martinez AM, Martinez A

Institution

Centre National de la Recherche Scientifique Unité Mixte de Recherche 6293/Institut National de la Santé et de la Recherche Médicale U1103–Génétique, Reproduction et Développement, Clermont Université, Aubière, France.

Source

Diabetes 61:11 2012 Nov pg 2796-806

MeSH

3T3-L1 Cells
Adipogenesis
Adipose Tissue, White
Adiposity
Aldehyde Reductase
Animals
Anti-Obesity Agents
Cell Size
Cloprostenol
Crosses, Genetic
Diet, High-Fat
Dinoprost
Disease Susceptibility
Down-Regulation
Insulin Resistance
Lipogenesis
Mice
Mice, 129 Strain
Mice, Inbred C57BL
Mice, Knockout
Molecular Targeted Therapy
Obesity

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22851578