Peroxisome Proliferator-Activated Receptor γ 2 Modulates Late-Pregnancy Homeostatic Metabolic Adaptations

• Main Authors: Yurena Vivas, Monica Díez-Hochleitner, Adriana Izquierdo-Lahuerta, Patricia Corrales, Daniel Horrillo, Ismael Velasco, Cristina Martínez-García, Mark Campbell, Julio Sevillano, Mercedes Ricote, Manuel Ros, Maria Pilar Ramos, Gema Medina-Gomez
• Format: Article
• Language: English
• Published: BMC 2016-10-01
• Series: Molecular Medicine
• Online Access: http://link.springer.com/article/10.2119/molmed.2015.00262

Abstract Pregnancy requires 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 γ (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 the liver. Lack of PPARγ2 provoked changes in the distribution of fat mass and preferentially prevented expansion of the perigonadal depot while at the same time exacerbating inflammation. Pregnant PPARγ2KO mice presented adipose tissue depot-dependent decreased expression of genes involved in lipid metabolism. Collectively, these data indicate that PPARγ2 is essential in promoting healthy adipose tissue expansion and immune and metabolic functionality during pregnancy, contributing to the physiological adaptations that lead gestation to term.