Maternal prenatal undernutrition programs adipose tissue gene expression in adult male rat offspring under high-fat diet

Abstract

-Several studies have shown that maternal undernutrition leading to low birth weight predisposes offspring to the development of metabolic pathologies such as obesity. Using a model of prenatal maternal 70% food restriction diet (FR30) in rat, we evaluated whether postweaning high-fat (HF) diet would amplify the phenotype observed under standard diet. We investigated biological parameters as well as gene expression profile focusing on white adipose tissues (WAT) of adult offspring. FR30 procedure does not worsen the metabolic syndrome features induced by HF diet. However, FR30HF rats displayed catch-up growth to match the body weight of adult control HF animals, suggesting an increase of adiposity while showing hyperleptinemia and a blunted increase of corticosterone. Using quantitative RT-PCR array, we demonstrated that FR30HF rats exhibited leptin and Ob-Rb as well as many peptide precursor and receptor gene expression variations in WAT. We also showed that the expression of genes involved in adipogenesis was modified in FR30HF animals in a depot-specific manner. We observed an opposite variation of STAT3 phosphorylation levels, suggesting that leptin sensitivity is modified in WAT adult FR30 offspring. We demonstrated that 11␤-HSD1, 11␤-HSD2, GR, and MR genes are coexpressed in WAT and that FR30 procedure modifies gene expression levels, especially under HF diet.

Is the adipose tissue a key target of developmental programming of adult adiposity by maternal undernutrition?

“…In particular, FR30N rats exhibited increased expression of several genes associated with de novo lipogenesis whereas no difference was observed in gene expression levels for gene involved in adipogenesis. 3 Our findings mirror the WAT transcriptional pattern described in a rat model of maternal protein restriction (MPR) throughout gestation and lactation. 7 In line, maternal 50% food restriction from 10 d to term gestation leads to adult intrauterine growth-restricted male rats that exhibited programmed upregulation of adipogenic transcription factor leading to hypertrophic adipocytes.…”

“…We then investigated tissue gene expression profile focusing on the WAT programmed mechanisms. 3 Most of the following results have been recently published.…”

The hypothalamus–adipose axis is a key target of developmental programming by maternal nutritional manipulation

“…Maternal reduced nutrition programmes an increase of fat cell size and number in the offspring. Adult rat offspring from LP dams (Guan et al 2005) and from FR70 dams during gestation (Lukaszewski et al 2011) showed enhanced adipogenesis (i.e. elevated PPARG activity) with impaired leptin antilipogenic action.…”

Adult glucose metabolism in extremely birthweight-discordant monozygotic twins

“…Support for this hypothesis has been provided by several studies. In rats, maternal undernutrition changed the gene expression profile that predisposes to altered fat deposition [6], whereas signs of increased oxidative stress and fibrosis were discovered in pancreatic islets in offspring of protein-restricted pregnant rats [7]. However, whether the association between early life factors and the development of type 2 diabetes is due to fetal programming or underlining common genetic and environmental influence remains debatable.…”