Expression Profile of Fatty Acid Metabolism Genes in Preimplantation Blastocysts of Obese and Non-Obese Mice

Abstract

Background: Recent studies have disclosed a close relationship between maternal obesity, fetal metabolism and pre- and postnatal development. The lipid metabolism in preimplantation embryos is a possible target of metabolic programming. Methods: 31 genes of beta-oxidation and fatty acid and cholesterol uptake, synthesis and regulation were analyzed in day 3.5 blastocysts from NZO (obese) and C57Bl/6 (normal weight) mice by RT-PCR and semiquantitative PCR. Results: The most obvious difference between both strains was the lack of the RXR gamma transcript in NZO blastocysts. In adult NZO mice, RXR gamma is detectable in most tissues. In a semiquantitative analysis, a higher transcription rate of fatty acid transport protein 4 (p = 0.004) and a reduced transcript number of fatty acid synthase (p = 0.049) was found in NZO blastocysts. Cholesterol synthesis regulation was modified in NZO blastocysts, as indicated by the ratio of sterol regulatory element-binding protein (SREBP) 2 / insulin-induced gene 1 (Insig 1) (p = 0.001). Conclusion: In mouse blastocysts enzymes and signal molecules of fatty acid and cholesterol metabolism resemble those expressed postnatally. Distinct differences in transcription rates of genes between blastocysts from obese and non-obese mothers indicate that preimplantation embryo development is an early target for metabolic programming.

UDP-Glucuronosyltransferase 1a Enzymes Are Present and Active in the Mouse Blastocyst

“…This was further confirmed when the obligate cofactor transporter for UGTs (the UDPGA transporter) was shown to be encoded on the fringe connection frc gene and involved in the Wingless, Hedgehog, fibroblast, and Notch signaling pathways in mice (Goto et al, 2001;Selva et al, 2001). Others have also demonstrated that the nuclear receptors retinoic X receptor (Königsdorf et al, 2012), peroxisome proliferator-activated receptor, subtype d (Kang et al, 2011), and hepatic nuclear factor 4 (Duncan et al, 1994) are present in preimplantation murine embryos. Speculatively, the actions of these receptors could be driving Ugt expression in mouse blastocysts, because Ugts/UGTs are responsive to these receptors.…”

Palmitate activation by fatty acid transport protein 4 as a model system for hepatocellular apoptosis and steatosis

“…While FATP4 has a unique property in activating VLFCA, such as lignoceric acid 24:0 [6,[9][10][11] and cerotic acid 26:0 [6], it has a weaker activity towards palmitate 16:0 (Pal) as demonstrated by various experimental systems including FATP4-overexpressed COS-1 cells [6], purified FATP4 protein [11] as well as the intestine [6,11], skin [11], and isolated skin fibroblasts [10] of FATP4-deficient mice. Since activation of saturated fatty acids, such as Pal, contributes to hepatocyte apoptosis, we hypothesize that FATP4's ability to generate palmitoyl-CoA may be involved in apoptosis.…”

“…With the FATP4 localization in the ER and MAM in various cell types [3,9,10], FATP4 may activate palmitoyl-CoA leading to an alteration in lipid metabolism, ER-stress and subsequently apoptosis. Because FATP4 is broadly distributed in multiple metabolic active tissues such as adipose tissue, FATP4 has been shown to alter the programming from obese mouse mothers to preimplantation embryos [16], and is correlated with insulin resistance [17] and obesity [18]. While FATP4 is a minor FATP in the liver, we had chosen FATP4 as a representative enzyme for other ACSs and FATPs to determine whether it can mediate the typical Pal activation which would lead to apoptosis and well-defined lipid metabolism corresponding to its localization.…”

Desorption Electrospray Ionization Mass Spectrometry Reveals Lipid Metabolism of Individual Oocytes and Embryos

“…Expression of FA synthase (FASN) was significantly reduced in blastocysts from obese mice, and was associated to changes in Chol synthesis regulation, indicating the physiological importance of enzymes and signaling molecules involved in FA and Chol metabolism in postnatal cellular programming [34]. Moreover, recent findings revealed marked differences in the regulation of Chol biosynthesis, sterol synthesis, and cell differentiation when bovine embryos produced in vivo were compared to their in vitro derived counterparts [35].…”