Rodriguez-Cruz Maricela, Sánchez Raúl, Sánchez Apolos M, Kelleher Shannon L, Sánchez-Muñoz Fausto, Maldonado Jorge, López-Alarcón Mardia
Laboratorio de Biología Molecular, Unidad de Investigación Médica en Nutrición, Hospital de Pediatría, Centro Medico Nacional Siglo XXI, IMSS, Mexico City, Mexico.
Biochim Biophys Acta. 2011 Apr;1811(4):284-93. doi: 10.1016/j.bbalip.2011.01.007. Epub 2011 Feb 1.
Metabolic adaptations are triggered in the maternal organism to synthesize milk with an adequate concentration of long-chain polyunsaturated fatty acids (LC-PUFAs) required to the newborn. They may be a high uptake of dietary linoleic acid and its conversion to LC-PUFAs by desaturases of fatty acids (FADS) 1 and 2 in the mammary gland (MG). It is unknown if they also occur from onset of pregnancy. The aim of this study was to explore the participation of the MG as a mechanism involved in LC-PUFAs synthesis to support their demand during pregnancy and lactation in rats. The expression of desaturases in MG was significantly (P<0.05) higher (12.3-fold for FADS1 and 41.2-fold for FADS2) during the late pregnancy and throughout lactation (31.7-fold for FADS1 and 67.1-fold higher for FADS2) than in nonpregnant rats. SREBF-1c showed a similar pattern of increase during pregnancy but remained higher only during the early lactation (11.7-fold, P<0.005). Transcript of ELOVL6 and FASN increased throughout pregnancy and lactation, respectively. ELOVL5 mRNA increased in MG only during lactation (2.8 to 5.3-fold, P<0.005). Accordingly, a higher content of LC-PUFAs was found in lactating MG than in nonpregnant rats. Results suggest that MG participates from late pregnancy and throughout lactation by expressing desaturases and elongases as a mechanism involved in LC-PUFAs synthesis, probably by SREBF-1c. Because desaturases and ELOVL5 were expressed in cultured lactocytes and such expression was downregulated by linoleic and arachidonic acid, these cells may be a useful model for understanding the regulatory mechanisms for LC-PUFAs synthesis in MG.
母体中会引发代谢适应,以合成含有新生儿所需适当浓度长链多不饱和脂肪酸(LC-PUFA)的乳汁。这些适应可能包括对膳食亚油酸的高摄取以及其在乳腺(MG)中通过脂肪酸去饱和酶(FADS)1和2转化为LC-PUFA。目前尚不清楚这些适应是否从怀孕开始就发生。本研究的目的是探讨乳腺作为参与LC-PUFA合成的机制,以支持大鼠在怀孕和哺乳期对其的需求。与未怀孕的大鼠相比,在怀孕后期和整个哺乳期,乳腺中去饱和酶的表达显著升高(P<0.05)(FADS1升高12.3倍,FADS2升高41.2倍),在整个哺乳期(FADS1升高31.7倍,FADS2升高67.1倍)。SREBF-1c在怀孕期间呈现类似的升高模式,但仅在哺乳早期保持较高水平(11.7倍,P<0.005)。ELOVL6和FASN的转录本在整个怀孕期和哺乳期分别增加。ELOVL5 mRNA仅在哺乳期乳腺中增加(2.8至5.3倍,P<0.005)。因此,在哺乳期乳腺中发现的LC-PUFA含量高于未怀孕的大鼠。结果表明,乳腺从怀孕后期到整个哺乳期通过表达去饱和酶和延长酶参与LC-PUFA的合成,可能是通过SREBF-1c。由于去饱和酶和ELOVL5在培养的乳腺细胞中表达,并且这种表达被亚油酸和花生四烯酸下调,这些细胞可能是理解乳腺中LC-PUFA合成调控机制的有用模型。