Abstract
Peri-conceptional exposure to maternal obesogenic nutrition is associated with in utero programming of later-life overweight and metabolic disease in the offspring. We aimed to investigate whether dietary intervention with a modified fatty acid quality in an obesogenic high-calorie (HC) diet during the preconception and gestational phases can improve unfavourable effects of an adipogenic maternal environment. In NMRI mice, peri-conceptional and gestational obesity was induced by feeding a HC diet (controls), and they were compared with dams on a fat-modified (Fat-mod) HC diet of the same energy content but enriched with medium-chain fatty acids (MCFAs) and adjusted to a decreased ratio of n-6 to n-3 long-chain polyunsaturated fatty acids (LC-PUFAs). Effects on maternal and placental outcomes at delivery (day 17.5 post coitum) were investigated. Despite comparable energy assimilation between the two groups of dams, the altered fatty acid composition of the Fat-mod HC diet induced lower maternal body weight, weights of fat depots, adipocyte size, and hepatic fat accumulation compared to the unmodified HC diet group. Further, there was a trend towards lower fasting glucose, insulin and leptin concentrations in dams fed the Fat-mod HC diet. Phenotypic changes were accompanied by inhibition of transcript and protein expression of genes involved in hepatic de novo lipogenesis comprising PPARG2 and its target genes Fasn, Acaca, and Fabp4, whereas regulation of other lipogenic factors (Srebf1, Nr1h3, Abca1) appeared to be more complex. The modified diet led to a sex-specific placental response by upregulating PPARG-dependent fatty acid transport gene expression in female versus male placentae. Qualitative modification of the fatty acid spectrum of a high-energy maternal diet, using a combination of both MCFAs and n-3 LC-PUFAs, seems to be a promising interventional approach to ameliorate the adipogenic milieu of mice before and during gestation.
Highlights
To date, up to two thirds of women in the reproductive age are overweight or obese in the United States [1]
Our data indicate that the unfavorable effects of an obesogenic high-energy diet on the maternal and gestational environment can be attenuated by a modification of the dietary fatty acid composition, applying a combination of medium-chain fatty acids (MCFAs) and n-3 LC-PUFAs before and during pregnancy
In our model of pregnant Naval Medical Research Institute (NMRI) dams, we found reduced liver fat accumulation following feeding of the Fat-mod HC diet compared to the HC diet
Summary
Up to two thirds of women in the reproductive age are overweight or obese in the United States [1]. We found that female Naval Medical Research Institute (NMRI) mice fed a high-calorie (HC) diet with 60% of energy from mainly saturated fat and a high sugar-to-starchratio presented with an increased weight at conception, an impaired glucose tolerance in pregnancy, and higher placental and offspring weights compared to control diet (CD)-fed dams [5]. We hypothesized that such adverse effects of the maternal obesogenic HC diet might be ameliorated or even prevented if the fat composition is altered via a combination of both an enrichment with MCFAs and a reduction of the n-6:n-3 LC-PUFA ratio. The aim was to evaluate the impact of a modification of the fatty acid quality of a HC diet during the peri-conceptional and gestational period of NMRI dams, by assessing maternal and placental outcomes at delivery
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