Background/Aims: Lipid metabolic disarray in the liver of young and adult mice offspring is induced by saturated fatty acids (SFA) but prevented by α-linolenic acid (ALA, 18:3 ω-3) in the maternal diet during pregnancy and lactation. The aim of the present study was to analyze the impact of maternal dietary ALA compared to an SFA diet on the liver gene expression in the newborn offspring. Methods: C57Bl6/J dams were fed with diets normal in calories but rich in ALA or SFA before mating and during pregnancy. Pups were sacrificed at birth and liver parameters were assessed. Gene expression was characterized by microarray analysis and validated by real-time quantitative PCR. Results: ALA, compared to SFA, in maternal diets during pregnancy increased polyunsaturated fatty acids, while it differentially modified fatty acid desaturase activities in offspring liver. Overall, 474 and 662 genes from the liver of newborn pups were differentially regulated by ALA and SFA compared to control diet (p < 0.05; fold change 2), respectively. Notably, Per3 was upregulated by ALA, whereas it was downregulated by SFA, compared to control diet. Conclusions: ALA- and SFA-enriched diets differentially affect the gene expression pattern in the offspring's liver. ALA, in particular, upregulates genes associated with low adiposity.

1.
Barker DJP: Fetal origins of coronary heart disease. BMJ 1995;311:171-174.
2.
Innis SM: Essential fatty acid transfer and foetal development. Placenta 2005;26:570-575.
3.
Mennitti LV, Oliveira JL, Morais CA, Estadella D, Oyama LM, do Nascimento CM, Pisani LP: Type of fatty acids in maternal diets during pregnancy and/or lactation and metabolic consequences of the offspring. J Nutr Biochem 2015;26:99-111.
4.
Shomonov-Wagner L, Raz A, Leikin-Frenkel A: Alpha linolenic acid in maternal diet halts the lipid disarray due to saturated fatty acids in the liver of mice offspring at weaning. Lipids Health Dis 2015;14:14.
5.
Hollander KS, Tempel Brami C, Konikoff FM, Fainaru M, Leikin-Frenkel A: Dietary enrichment with alpha-linolenic acid during pregnancy attenuates insulin resistance in adult offspring in mice. Arch Physiol Biochem 2014;120:99-111.
6.
Warensjö E, Sundström J, Vessby B, Cederholm T, Risérus U: Markers of dietary fat quality and fatty acid desaturation as predictors of total and cardiovascular mortality: a population-based prospective study. Am J Clin Nutr 2008;88:203-209.
7.
Katzenellenbogen M, Mizrahi L, Pappo O, Klopstock N, Olam D, Jacob-Hirsch J, Amariglio N, Rechavi G, Domany E, Galun E, Goldenberg D: Molecular mechanisms of liver carcinogenesis in the mdr2-knockout mice. Mol Cancer Res 2007;5:1159-1170.
8.
Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U, Speed TP: Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 2003;4:249-264.
9.
Huang DW, Sherman BT, Lempicki RA: Systematic and integrative analysis of large gene lists using DAVID Bioinformatics Resources. Nat Protoc 2009;4:44-57.
10.
Franceschini A, Szklarczyk D, Frankild S, Kuhn M, Simonovic M, Roth A, Lin J, Minguez P, Bork P, von Mering C, Jensen LJ: STRING v9.1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res 2013;41:D808-D815.
11.
Oliveros JC: VENNY. An interactive tool for comparing lists with Venn's diagrams. http://bioinfogp.cnb.csic.es/tools/venny/index.html.
12.
Juknat A, Pietr M, Kozela E, Rimmerman N, Levy R, Coppola G, Geschwind D, Vogel Z: Differential transcriptional profiles mediated by exposure to the cannabinoids cannabidiol and Δ9-tetrahydrocannabinol in BV-2 microglial cells. Br J Pharmacol 2012;165:2512-2528.
13.
Juknat A, Pietr M, Kozela E, Rimmerman N, Levy R, Gao F, Coppola G, Geschwind D, Vogel Z: Microarray and pathway analysis reveal distinct mechanisms underlying cannabinoid-mediated modulation of LPS-induced activation of BV-2 microglial cells. PLoS One 2013;8:e61462.
14.
Emery JA, Hermon K, Hamid NK, Donald JA, Turchini GM: Δ-6 desaturase substrate competition: dietary linoleic acid (18:2n-6) has only trivial effects on α-linolenic acid (18:3n-3) bioconversion in the teleost rainbow trout. PLoS One 2013;8:e57463.
15.
Teng KT, Chang CY, Chang LF, Nesaretnam K: Modulation of obesity-induced inflammation by dietary fats: mechanisms and clinical evidence. Nutr J 2014;13:12.
16.
Zheng J, Xiao X, Zhang Q, Yu M, Xu J, Wang Z: Maternal high-fat diet modulates hepatic glucose, lipid homeostasis and gene expression in the PPAR pathway in the early life of offspring. Int J Mol Sci 2014;15:14967-14983.
17.
Finck BN, Gropler MC, Chen Z, Leone TC, Croce MA, Harris TE, Lawrence JC Jr, Kelly DP: Lipin 1 is an inducible amplifier of the hepatic PGC-1α/PPAR α regulatory pathway. Cell Metab 2006;4:199-210.
18.
Kimmel AR, Sztalryd C: Perilipin 5, a lipid droplet protein adapted to mitochondrial energy utilization. Curr Opin Lipidol 2014;25:110-117.
19.
Wang C, Zhao Y, Gao X, Li L, Yuan Y, Liu F, Zhang L, Wu J, Hu P, Zhang X, Gu Y, Xu Y, Wang Z, Li Z, Zhang H, Ye J: Perilipin 5 improves hepatic lipotoxicity by inhibiting lipolysis. Hepatology 2015;61:870-882.
20.
Mauer J, Chaurasia B, Goldau J, Vogt MC, Ruud J, Nguyen KD, Theurich S, Hausen AC, Schmitz J, Brönneke HS, Estevez E, Allen TL, Mesaros A, Partridge L, Febbraio MA, Chawla A, Wunderlich FT, Brüning JC: Signaling by IL-6 promotes alternative activation of macrophages to limit endotoxemia and obesity-associated resistance to insulin. Nat Immunol 2014;15:423-430.
21.
Costa MJ, So AY, Kaasik K, Krueger KC, Pillsbury ML, Fu YH, Ptacek LJ, Yamamoto KR, Feldman BJ: Circadian rhythm gene period 3 is an inhibitor of the adipocyte cell fate. J Biol Chem 2011;286:9063-9070.
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