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Transgenic increase in N-3/n-6 Fatty Acid ratio reduces maternal obesity-associated inflammation and limits adverse developmental programming in mice.

ABSTRACT: Maternal and pediatric obesity has risen dramatically over recent years, and is a known predictor of adverse long-term metabolic outcomes in offspring. However, which particular aspects of obese pregnancy promote such outcomes is less clear. While maternal obesity increases both maternal and placental inflammation, it is still unknown whether this is a dominant mechanism in fetal metabolic programming. In this study, we utilized the Fat-1 transgenic mouse to test whether increasing the maternal n-3/n-6 tissue fatty acid ratio could reduce the consequences of maternal obesity-associated inflammation and thereby mitigate downstream developmental programming. Eight-week-old WT or hemizygous Fat-1 C57BL/6J female mice were placed on a high-fat diet (HFD) or control diet (CD) for 8 weeks prior to mating with WT chow-fed males. Only WT offspring from Fat-1 mothers were analyzed. WT-HFD mothers demonstrated increased markers of infiltrating adipose tissue macrophages (P<0.02), and a striking increase in 12 serum pro-inflammatory cytokines (P<0.05), while Fat1-HFD mothers remained similar to WT-CD mothers, despite equal weight gain. E18.5 Fetuses from WT-HFD mothers had larger placentas (P<0.02), as well as increased placenta and fetal liver TG deposition (P<0.01 and P<0.02, respectively) and increased placental LPL TG-hydrolase activity (P<0.02), which correlated with degree of maternal insulin resistance (r?=?0.59, P<0.02). The placentas and fetal livers from Fat1-HFD mothers were protected from this excess placental growth and fetal-placental lipid deposition. Importantly, maternal protection from excess inflammation corresponded with improved metabolic outcomes in adult WT offspring. While the offspring from WT-HFD mothers weaned onto CD demonstrated increased weight gain (P<0.05), body and liver fat (P<0.05 and P<0.001, respectively), and whole body insulin resistance (P<0.05), these were prevented in WT offspring from Fat1-HFD mothers. Our results suggest that reducing excess maternal inflammation may be a promising target for preventing adverse fetal metabolic outcomes in pregnancies complicated by maternal obesity.

SUBMITTER: Heerwagen MJ

PROVIDER: S-EPMC3692451 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Transgenic increase in N-3/n-6 Fatty Acid ratio reduces maternal obesity-associated inflammation and limits adverse developmental programming in mice.

Heerwagen Margaret J R MJ Stewart Michael S MS de la Houssaye Becky A BA Janssen Rachel C RC Friedman Jacob E JE

PloS one 20130625 6

Maternal and pediatric obesity has risen dramatically over recent years, and is a known predictor of adverse long-term metabolic outcomes in offspring. However, which particular aspects of obese pregnancy promote such outcomes is less clear. While maternal obesity increases both maternal and placental inflammation, it is still unknown whether this is a dominant mechanism in fetal metabolic programming. In this study, we utilized the Fat-1 transgenic mouse to test whether increasing the maternal ...[more]

PMID: 23825686

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Project description:Abstract Objectives Fatty acid esters of hydroxy fatty acids (FAHFAs) are a novel class of endogenous lipids with suspected anti-inflammatory and anti-diabetic properties in adults. They have been reported to be present in breast milk (BM), but there is no data about their role in infant growth and nutrition. Our objective was to determine the role of maternal body mass index (BMI) on BM FAHFA composition and to delineate the association of these BM fatty acids on infant growth and adiposity. Methods This is a secondary analysis of a randomized controlled trial of maternal vitamin D supplementation during lactation (NCT00412074). We included 40 control mother-infant dyads who had BM samples at one (V1) and four (V4) months and outcome data available. At V1 and V4, maternal and infant anthropometrics were measured, dual energy absorptiometry (DXA) scans conducted, and BM samples collected. BM lipids were measured using established methods of UHPLC-C30RP/HRAM mass spectrometry. Our primary infant growth outcomes were percentage of fat and lean mass, fat mass index, and fat-free mass index. Redundancy analysis (RDA) was used to analyze the relation between individual lipids, maternal BMI, and infant growth. Focusing on V1 measurements, we computed the unadjusted associations between maternal BMI with BM lipids; BM lipids with infant growth using Pearson's correlations; and the adjusted associations of BM lipids at V1 with infant growth using linear regression with adjustment for relevant covariates. Results The mean maternal BMI was 29 kg/m2. There was no correlation between maternal BMI and reported dietary intake of fat. Higher maternal BMI was associated with a higher concentration of saturated and monounsaturated FAHFAs, and a lower concentration of polyunsaturated FAHFAs in BM at V1. In an unadjusted model, saturated and monounsaturated FAHFAs were associated with higher infant fat mass and lower lean mass. The converse was seen with polyunsaturated FAHFAs which were associated with lower infant fat mass and higher lean mass. In a fully adjusted model, these associations were attenuated but the overall pattern persisted (Table 1). Conclusions Maternal BMI influences the FAHFA composition of BM. In turn, BM FAHFA composition may play a role in programming infant growth patterns. Funding Sources The Nutritional Obesity Research Consortium Grant. Supporting Tables, Images and/or Graphs

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Transgenic increase in N-3/n-6 Fatty Acid ratio reduces maternal obesity-associated inflammation and limits adverse developmental programming in mice.

Publications

Transgenic increase in N-3/n-6 Fatty Acid ratio reduces maternal obesity-associated inflammation and limits adverse developmental programming in mice.

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