title: Peroxisome proliferator activated receptor gamma 2 modulates late pregnancy homeostatic metabolic adaptations.
abstract: Pregnancy requires the adaptation of maternal energy metabolism including expansion and functional modifications of adipose tissue. Insulin resistance (IR), predominantly during late gestation, is a physiological metabolic adaptation that serves to support the metabolic demands of fetal growth. The molecular mechanisms underlying these adaptations are not fully understood and may contribute to gestational diabetes mellitus. Peroxisome proliferator-activated receptor gamma (PPARγ) controls adipogenesis, glucose and lipid metabolism and insulin sensitivity. The PPARγ2 isoform is mainly expressed in adipocytes and is thus likely to contribute to adipose tissue adaptation during late pregnancy. In the present study, we investigated the contribution of PPARγ2 to the metabolic adaptations occurring during the late phase of pregnancy in the context of IR. Using a model of late pregnancy in PPARγ2 knockout (KO) mice, we found that deletion of PPARγ2 exacerbated IR in association with lower serum adiponectin levels, increased body weight and enhanced lipid accumulation in liver. Lack of PPARγ2 provoked changes in the distribution of fat mass and preferentially prevented the expansion of the perigonadal depot while at the same time exacerbating inflammation. PPARγ2KO pregnant mice presented adipose tissue depot-dependent decreased expression of genes involved in lipid metabolism. Collectively, these data indicate that PPARγ2 is essential to promote healthy adipose tissue expansion and immune and metabolic functionality during pregnancy, contributing to the physiological adaptations that lead gestation to term.
authors: University Rey Juan Carlos, Department of Basic Sciences of Health, Area of Biochemistry and Molecular Biology, Avda. de Atenas s/n, Alcorcon, 28922 Madrid, Spain.
authors: Yurena
authors: Y
authors: Vivas
authors: University Rey Juan Carlos, Department of Basic Sciences of Health, Area of Biochemistry and Molecular Biology, Avda. de Atenas s/n, Alcorcon, 28922 Madrid, Spain.|Faculty of Pharmacy, University San Pablo-CEU, Carretera Boadilla del Monte, km 5.3, 28668 Madrid, Spain.
authors: Monica
authors: M
authors: Díez-Hochleitner
authors: University Rey Juan Carlos, Department of Basic Sciences of Health, Area of Biochemistry and Molecular Biology, Avda. de Atenas s/n, Alcorcon, 28922 Madrid, Spain.
authors: Adriana
authors: A
authors: Izquierdo-Lahuerta
authors: University Rey Juan Carlos, Department of Basic Sciences of Health, Area of Biochemistry and Molecular Biology, Avda. de Atenas s/n, Alcorcon, 28922 Madrid, Spain.
authors: Patricia
authors: P
authors: Corrales
authors: University Rey Juan Carlos, Department of Basic Sciences of Health, Area of Biochemistry and Molecular Biology, Avda. de Atenas s/n, Alcorcon, 28922 Madrid, Spain.
authors: Daniel
authors: D
authors: Horrillo
authors: University Rey Juan Carlos, Department of Basic Sciences of Health, Area of Biochemistry and Molecular Biology, Avda. de Atenas s/n, Alcorcon, 28922 Madrid, Spain.
authors: Ismael
authors: I
authors: Velasco
authors: University Rey Juan Carlos, Department of Basic Sciences of Health, Area of Biochemistry and Molecular Biology, Avda. de Atenas s/n, Alcorcon, 28922 Madrid, Spain.
authors: Cristina
authors: C
authors: Martínez-García
authors: Metabolic Research Laboratories, Level 4, Institute of Metabolic Science, Box 289, Addenbrooke's Hospital, University of Cambridge, CB2 0QQ, UK.
authors: Mark
authors: M
authors: Campbell
authors: Faculty of Pharmacy, University San Pablo-CEU, Carretera Boadilla del Monte, km 5.3, 28668 Madrid, Spain.
authors: Julio
authors: J
authors: Sevillano
authors: National Center of Cardiovascular Research Carlos III (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
authors: Mercedes
authors: M
authors: Ricote
authors: University Rey Juan Carlos, Department of Basic Sciences of Health, Area of Biochemistry and Molecular Biology, Avda. de Atenas s/n, Alcorcon, 28922 Madrid, Spain.
authors: Manuel
authors: M
authors: Ros
authors: Faculty of Pharmacy, University San Pablo-CEU, Carretera Boadilla del Monte, km 5.3, 28668 Madrid, Spain.
authors: Maria Pilar
authors: MP
authors: Ramos
authors: University Rey Juan Carlos, Department of Basic Sciences of Health, Area of Biochemistry and Molecular Biology, Avda. de Atenas s/n, Alcorcon, 28922 Madrid, Spain.|MEMORISM Research Unit of University Rey Juan Carlos- Institute of Biomedical Research "Alberto Sols" (CSIC).
authors: Gema
authors: G
authors: Medina-Gomez
keywords: Insulin resistance; PPARγ; adiponectin; adipose tissue; diabetes; gestation; inflammation