Protein restriction during pregnancy affects maternal liver lipid metabolism and fetal brain lipid composition in the rat

Abstract

Protein restriction during pregnancy affects maternal liver lipid metabolism and fetal brain lipid composition in the rat. Am J Physiol Endocrinol Metab 298: E270 -E277, 2010. First published November 17, 2009 doi:10.1152/ajpendo.00437.2009.-Suboptimal developmental environments program offspring to lifelong metabolic problems. The aim of this study was to determine the impact of protein restriction in pregnancy on maternal liver lipid metabolism at 19 days of gestation (dG) and its effect on fetal brain development. Control (C) and restricted (R) mothers were fed with isocaloric diets containing 20 and 10% of casein. At 19 dG, maternal blood and livers and fetal livers and brains were collected. Serum insulin and leptin levels were determinate in mothers. Maternal and fetal liver lipid and fetal brain lipid quantification were performed. Maternal liver and fetal brain fatty acids were quantified by gas chromatography. In mothers, liver desaturase and elongase mRNAs were measured by RT-PCR. Maternal body and liver weights were similar in both groups. However, fat body composition, including liver lipids, was lower in R mothers. A higher fasting insulin at 19 dG in the R group was observed (C ϭ 0.2 Ϯ 0.04 vs. R ϭ 0.9 Ϯ 0.16 ng/ml, P Ͻ 0.01) and was inversely related to early growth retardation. Serum leptin in R mothers was significantly higher than that observed in C rats (C ϭ 5 Ϯ 0.1 vs. R ϭ 7 Ϯ 0.7 ng/ml, P Ͻ 0.05). In addition, protein restriction significantly reduced gene expression in maternal liver of desaturases and elongases and the concentration of arachidonic (AA) and docosahexanoic (DHA) acids. In fetus from R mothers, a low body weight (C ϭ 3 Ϯ 0.3 vs. R ϭ 2 Ϯ 0.1 g, P Ͻ 0.05), as well as liver and brain lipids, including the content of DHA in the brain, was reduced. This study showed that protein restriction during pregnancy may negatively impact normal fetal brain development by changes in maternal lipid metabolism.programming; development; docosahexaenoic acid; arachidonic acid HUMAN EPIDEMIOLOGICAL (28, 31) and experimental animal studies (16,23,25) have shown that a suboptimal environment either in the womb or early in the neonatal life alters growth and predisposes individuals to lifelong health problems. Maternal dietary deficiencies in pregnancy result in multiple adverse outcomes in the offspring (3, 12). Fetal growth depends mostly on the amount and type of nutrients obtained from the mother. Therefore, the mother must adapt her metabolism to support this continuous draining of substrates. The effects of an altered intrauterine environment can be passed transgenerationally by epigenetic mechanisms involving changes in gene expression (41). During late gestation, maternal liver plays a central role in whole body lipid metabolism. Maternal triglycerides (TG) are not transported intact across the placenta, whereas free fatty acids (FAs), including longchain polyunsaturated fatty acids (LC-PUFAs), can be transported (32). Therefore, a deficient maternal FA intake, particularly essential FAs (...

Programming the brain: Common outcomes and gaps in knowledge from animal studies of IUGR

“…There is also considerable variability in the length, degree and timing of nutritional restriction 151 between studies [79][80][81][82][83][84][85][86][87][88], with some studies restricting throughout gestation or the entire length of 152 pregnancy studied [79,82,86,89], whilst others may only restrict during part of gestation [80,83,153 84, 88], or extend maternal nutrient restriction into lactation [85,87]. The patterns of restriction in 154 these models also differ from that in human IUGR due to placental insufficiency, which 155 progressively worsens during pregnancy [ Figure 2,14].…”

“…Diagram does not show representative of the timing described in the literature: rat UPL [112,115] the variety of timing used in these studies they are not shown above. Fetal weight ↓13% [199] ↓5-35% [86,104,200] ↑7-25% [201] = [80] [82] ↓11% [82] ↓ [128] ↓8-31% [112 , 202-204] = E19, ↓E21 [160] ↓22-63% [106, 119, 121, 142-144, 161, 162, 205-207] ↓20-36% [102,208,209] ↓20-42% [108,109,111] ↓15-43% [11,107,210,211] Placental weight ↓9.5-35% [104,200] = [86] ↑↓ during pregnancy [201] = [89] ↓size as pregnancy progresses [82] ↓20% [202] ↓21-40% [106, 142-144, 161, 206] = [102,208] ↓44% [212] ↓35% [109] ↓36-64% [11,107,132,210,211] Fetal brain size = [86] ↑12% [201] ↓E90, = E135 [82] =E16, E18 [128] ↓E20 …”

Experimental diet based on the foods listed in the Family Budget Survey is more detrimental to growth than to the reflex development of rats

“…Rats. [grupo-controle: 12,00 (9,(0)(1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)00) dias; POFG=9,50 (9,(0)(1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)00) dias] e queda livre [grupo-controle:18,00 (17,00); POFG=16,00 (13,(0)(1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)…”

“…According to Torres et al 10 , moderate protein restriction (10%) reduces the amount of Arachidonic Acid and Docosahexaenoic Acid (DHA) in the dam's liver, along with the enzymes that elongate and desaturate essential fatty acids, resulting in lower fat content in the fetal brain. Marin et al 33 then showed that these events are minimized when dietary fat consists of soybean oil, even if protein content is below 5%.…”

Os efeitos do estresse na função do eixo hipotalâmico-pituitário-adrenal em indivíduos com esquizofrenia

“…Other studies have shown that restriction of protein intake during pregnancy may have a negative effect on fetal brain development. This is thought to be due to changes in maternal metabolism of lipids, which are an essential component of cellular membranes 39 . Interestingly, the behavioural abnormalities seen in these protein restricted models do not manifest until early adulthood, including effects on brain-regulated activities such as decreased pre-pulse inhibition of the startle response and hyperlocomotion, which are traditionally used as a measure of schizophrenia-like behavior 40,41 .…”