Modification of the fatty acid composition of an obesogenic diet improves the maternal and placental metabolic environment in obese pregnant mice

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.

Maternal Obesity: A Focus on Maternal Interventions to Improve Health of Offspring

“…While most studies in rodents involve diet-induced obesogenic effects, alteration in the chemistry of a high-calorie (HC) obesogenic diet itself can affect offspring metabolic health. A study compared modified fatty acid (HC diet of equivalent energy but with large proportion of medium-chain fatty acids and lower ratio of n-6/ n-3 PUFAs to regular HC diet ( 87 ). Lower GWG and reduced hepatic fat accumulation were observed in the modified fatty acid diet group compared to the regular HC diet.…”

MicroRNA-33a-5p sponges to inhibit pancreatic β-cell function in gestational diabetes mellitus LncRNA DANCR

“…A high level of ABCA1 was observed in the endothelial cells of fetal capillaries on the maternal side of the placenta [35,36]. ABCA1 regulates the transplacental feto-maternal lipid exchange implying its important role in normal fetal development [37]. ABCA1 was also reported to be downregulated in GDM patients [38].…”

Comparative Study of PPARγ Targets in Human Extravillous and Villous Cytotrophoblasts

“…The majority of the terms recovered in our analysis were consistent with reports from the existing literature. For example, the terms "long-chain fatty-acyl-CoA biosynthetic process," "regulation of plasma lipoprotein particle levels," "plasma 12 PPAR Research lipoprotein remodeling," and "PPAR signaling pathway" are all associated with "fatty acid transport," which in the placenta is known to demonstrate sex-specific differences due to the PPARγ-dependent response of genes involved in lipogenesis [34]. Signaling molecules and dynamic regulation of the cytoskeleton are required in trophoblast invasion [35][36][37], which are related to such terms as "regulation of epithelial cell migration," "regulation of actin cytoskeleton," and "tight junction."…”