'The Feinstein Institute for Medical Research (North Shore LIJ Research Institute)'
Doi
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.This work was supported by grants
from the Spanish Ministry of Economy and
Competitiveness: BFU2012-33594 and
BFU2013-47384-R to GMG; SAF2015-
64287-R to M. Ricote; and SAF2014-56671-R
to MPR; predoctoral fellowship BES-2010-
038107 to YV; and grants S2010/BMD-2423
from the Community of Madrid to MPR
and GMG. The authors thank Saverio Cinti
for his helpful comments with histological
samples, Antonio Vidal-Puig for his help
in discussion and Lucia Torres for technical
assistance.S
