Maternal high-fructose intake during pregnancy and lactation induces metabolic syndrome in adult offspring

BACKGROUND/OBJECTIVESNutritional status and food intake during pregnancy and lactation can affect fetal programming. In the current metabolic syndrome epidemic, high-fructose diets have been strongly implicated. This study investigated the effect of maternal high-fructose intake during pregnancy and lactation on the development of metabolic syndrome in adult offspring.SUBJECTS/METHODSDrinking water with or without 20% fructose was administered to female C57BL/6J mice over the course of their pregnancy and lactation periods. After weaning, pups ate regular chow. Accu-Chek Performa was used to measure glucose levels, and a tail-cuff method was used to examine systolic blood pressure. Animals were sacrificed at 7 months, their livers were excised, and sections were stained with Oil Red O and hematoxylin and eosin (H&E) staining. Kidneys were collected for gene expression analysis using quantitative real-time Polymerase chain reaction.RESULTSAdult offspring exposed to maternal high-fructose intake during pregnancy and lactation presented with heavier body weights, fattier livers, and broader areas under the curve in glucose tolerance test values than control offspring. Serum levels of alanine aminotransferase, aspartate aminotransferase, glucose, triglycerides, and total cholesterol and systolic blood pressure in the maternal high-fructose group were higher than that in controls. However, there were no significant differences in mRNA expressions of renin-angiotensin-aldosterone system genes and sodium transporter genes.CONCLUSIONSThese results suggest that maternal high-fructose intake during pregnancy and lactation induces metabolic syndrome with hyperglycemia, hypertension, and dyslipidemia in adult offspring.     

Hydrogenated fat diet intake during pregnancy and lactation modifies the PAI-1 gene expression in white adipose tissue of offspring in adult life

We examine whether feeding pregnant and lactating rats hydrogenated fats rich in trans fatty acids modifies the plasma lipid profiles and the expression of adipokines involved with insulin resistance and cardiovascular disease in their 90-day-old offspring. Pregnant and lactating Wistar rats were fed with either a control diet (C group) or one enriched with hydrogenated vegetable fat (T group). Upon weaning, the male pups were sorted into four groups: CC, mothers were receiving C and pups were kept on C; CT, mothers were receiving C and pups were fed with T; TT, mothers were receiving T and pups were kept on T; TC, mothers were receiving T and pups were fed with C. Pups' food intake and body weight were quantified weekly and the pups were killed at day 90 of life by decapitation. Blood and carcass as well as retroperitoneal, epididymal, and subcutaneous white adipose tissues were collected. Food intake and body weight were lower in TC and TT, and metabolic efficiency was reduced in TT. Offspring of TT and TC rats had increased white adipose tissue PAI-1 gene expression. Insulin receptor was higher in TT than other groups. Ingestion of hydrogenated vegetable fat by the mother during gestation and lactation could promote deleterious consequences, even after the withdrawal of the causal factor.     

Maternal intake of fatty acids during pregnancy and allergies in the offspring

Fatty acids (FA) are known to have a number of immunological effects and, accordingly, may play a role in the development of allergic diseases. We investigated the effect of maternal intake of FA during pregnancy on the risk of allergic rhinitis, wheeze and atopic eczema in children aged 5 years. The present study analysed data from the Finnish Type 1 Diabetes Prediction and Prevention Nutrition Study, a population-based birth cohort study with a 5-year follow-up. Complete information on maternal diet (assessed by a validated FFQ) and International Study of Asthma and Allergies in Childhood-based allergic outcomes was available for 2441 children. Cox proportional regression and logistic regression were used for the analyses. After adjusting for potential confounding variables, high maternal consumption of butter and butter spreads (hazard ratio (HR) 1.33; 95 % CI 1.03, 1.71) and higher ratio of n-6:n-3 FA (HR 1.37; 95 % CI 1.07, 1.77) during pregnancy were associated with an increased risk of allergic rhinitis in the offspring by 5 years of age. High maternal intakes of total PUFA (HR 0.71; 95 % CI 0.52, 0.96) and α-linolenic FA (HR 0.73; 95 % CI 0.54, 0.98) were associated with a decreased risk of allergic rhinitis. However, these results lost their significance after adjustment for multiple comparisons. Overall, our data suggest that maternal consumption of butter, the ratio of n-6:n-3 FA and intake of PUFA and α-linolenic FA during pregnancy may be potential determinants of allergic rhinitis in the offspring.     

Estimation of body fat in healthy Swedish women during pregnancy and lactation

Reliable estimates of changes in body fat are important in studies of energy requirements during human reproduction. It is not known if current methods for the estimation of total body fat (TBF) are adequate for this purpose. In this paper earlier reported data from 29 women are used to show how methodology affects estimates of changes in TBF during reproduction. Skinfold thicknesses are also reported and equations relating these measurements to TBF were developed and used to demonstrate how well the skinfold technique could estimate such changes. No correlation was found between changes in body weight and body fat during early pregnancy or between the maternal changes in body weight and body fat over the complete pregnancy. These findings are tentatively explained by changes in the degree of hydration of the body.     

Maternal low-protein diet during lactation programmes body composition and glucose homeostasis in the adult rat offspring

Previously we have reported that maternal malnutrition during lactation programmes body weight and thyroid function in the adult offspring. In the present study we evaluated the effect of maternal protein restriction during lactation upon body composition and hormones related to glucose homeostasis in adult rats. During lactation, Wistar lactating rats and their pups were divided into two experimental groups: control (fed a normal diet; 23% protein) and protein-restricted (PR; fed a diet containing 8% protein). At weaning, offspring received a normal diet until they were 180 d old. Body weight (BW) and food intake were monitored. Serum, adrenal glands, visceral fat mass (VFM) and carcasses were collected. PR rats showed lower BW (-13%; P < 0.05), VFM (-33%; P < 0.05), total body fat (-33%; P < 0.05), serum glucose (-7%; P < 0.05), serum insulin (-26%, P < 0.05), homeostasis model assessment index (-20%), but higher total adrenal catecholamine content (+90%; P < 0.05) and serum corticosterone concentration (+51%; P < 0.05). No change was observed in food intake, protein mass or total body water. The lower BW of PR rats is due to a reduction of white fat tissue, probably caused by an increase in lipolysis or impairment of lipogenesis; both effects could be related to higher catecholaminergic status, as well as to hypoinsulinaemia. To conclude, changes in key hormones which control intermediary metabolism are programmed by maternal protein restriction during lactation, resulting in BW alterations in adult rats.     

孕期及哺乳期n-6/n-3脂肪酸变化对仔鼠脑源性神经营养因子基因表达的影响

目的 探讨孕期及哺乳期n-3 多不饱和脂肪酸(n-3 polyunsaturated fatty acids,n-3 PUFAs)摄入量及其与n-6 PUFAs比例对仔鼠脑源性神经营养因子(brain-derived neurotrophic factor,bdnf)基因表达的影响。方法 使用6~8周龄清洁级C57BL/6J雌性小鼠,随机分为5 组,分别给予n-3 PUFAs缺乏和4种不同含量n-3 PUFAs(n-6/n-3 PUFAs比值分别为15∶1、5∶1、1∶1及1∶5)饲料喂养。小鼠12~14周龄时雌雄合笼交配繁殖,仔鼠断乳后继续行母鼠相同饲料喂养,分别在生后7 d、21 d和3 月时被处死后取脑。同时,分别从n-3 PUFAs缺乏组和n-6/n-3 PUFAs(5∶1)组中选取等量仔鼠,21 d断乳后相互交换饲料喂养至3个月,处死后取脑。采用实时荧光定量PCR技术测定脑皮质bdnf基因mRNA的表达。结果 与n-3 PUFAs缺乏饲料组相比,对于7 d和21 d幼年仔鼠,只有n-6/n-3 PUFAs(1∶5)饲料组bdnf基因mRNA表达量显著升高;对于3 月龄成年仔鼠,各含n-3 PUFAs饲料组bdnf基因mRNA的表达均升高。对于孕期和哺乳期n-3 PUFAs缺乏饲料组仔鼠,断乳后给予含n-3 PUFAs饲料喂养未能提升脑皮质bdnf基因mRNA表达;而孕期和哺乳期含n-3 PUFAs饲料喂养的仔鼠,断乳后给予n-3 PUFAs缺乏饲料喂养时,脑皮质bdnf基因mRNA表达量见一定程度的升高。结论 孕期及哺乳期可能需要较高的n-3 PUFAs摄入,才能满足幼年期诱导脑bdnf表达之需。保证生命早期n-3 PUFAs的适量摄入,有助于维持成年期bdnf的正常表达。     

Olive oil consumption during pregnancy and lactation in rats influences mammary cancer development in female offspring

This study examined the effects of variety and quantity of dietary fat consumed by rats during pregnancy and lactation on female offspring's response to chemically induced mammary cancer. Groups of six female rats were fed diets containing 7% corn oil (7-CO), 15% CO (15-CO), 7% olive oil (7-OO), or 15% OO (15-OO) for 5 wk prior to, and during, pregnancy and lactation. Female offspring (n = 15 per group) were fed a 7-CO diet, and mammary cancer was induced with 7,12-dimethylbenz[a]anthracene (DMBA). Three months following cancer induction tumor incidence and size were recorded, and markers of apoptosis, serum estrogen concentrations, and hepatic phase II enzymes were measured. Tumor incidence was 47% in offspring born to mothers fed the 7-OO diet, rose to 67% in 7-CO and 15-OO offspring, and reached 86% in 15-CO. A trend toward smaller tumors was observed in the 7-OO group, and offspring of mothers fed high-fat diets had significantly more tumors. Estradiol levels at the end of lactation were significantly lower in mothers fed 7-OO but were similar in all groups of offspring. In tumor tissue, Bcl-2 expression was highest in the 15-CO offspring, and Bak expression was significantly higher in rats exposed to OO. A distinct trend toward increased caspase-3 expression (20 kDa) was observed in the 7-OO offspring, and both low-fat diets significantly elevated caspase activity. In healthy mammary tissue, rats exposed to low-fat diets had significantly higher caspase-3 (32-kDa) levels, and caspase-3 activity was significantly higher in the healthy tissue from both OO groups. Hepatic quinone reductase activity was significantly lower in offspring of mothers fed the low-fat diets. These results indicate that perinatal exposure to OO may have a protective effect against future development of mammary cancer in female offspring, whereas high-fat diets fed to pregnant and lactating rats, in particular CO, may be deleterious.     

哺乳期母体接触氯氰菊酯对子代雌鼠学习记忆的损害效应

目的 研究哺乳期母鼠接触氯氰菊酯对子代成年雌鼠学习记忆能力的损害作用及其可能机制.方法 12只ICR母鼠随机分成对照组、6.25和25.00 mg/kg染毒组(每组4只母鼠,每窝10只仔鼠,雌雄各半,即每组20只雌鼠),于子代雌鼠出生后第1～21天(PNDl～ PND21),每天经口灌胃给予母鼠氯氰菊酯(6.25和25.00 mg/kg)染毒1次,对照组母鼠给予玉米油.染毒后39d,采用六臂放射状水迷 宫检测PND60雌鼠的学习记忆能力.检试结束后,称体重,处死动物取脑称重并分离海马组织,用蛋白质免疫印迹(Western blotting)法检测海马中N-甲基-D-门冬氨酸(NMDA)受体NR1亚单位蛋白表达水平.结果 各组子代雌鼠体重和脑重的差异无统计学意义(P＞0.05).经重复测量资料方差分析显示,在学习期,25.00 mg/kg染毒组子代雌鼠潜伏期[(31.3±17.0)s]长于对照组[(21.0±14.0)s];在记忆期,25.00 mg/kg染毒组子代雌鼠潜伏期[(24.6±21.1)s]较对照组[(14.1±16.3)s]延长,差异均有统计学意义(P＜0.05).各组子代雌鼠在学习期和记忆期的错误数比较,差异均无统计学(P＞0.05).与对照组相比,25.0 mg/kg染毒组子代雌鼠海马组织NR1蛋白表达水平明显降低,差异有统计学意义(P＜0.01).结论 哺乳期母鼠接触氯氰菊酯在一定程度上损伤子代成年雌鼠学习记忆能力,可能与海马组织中NR1亚单位蛋白表达水平下降有关.     

Fructose consumption during pregnancy and lactation induces fatty liver and glucose intolerance in rats

Nutritional insults during pregnancy and lactation are health risks for mother and offspring. Both fructose (FR) and low-protein (LP) diets are linked to hepatic steatosis and insulin resistance in nonpregnant animals. We hypothesized that dietary FR or LP intake during pregnancy may exacerbate the already compromised glucose homeostasis to induce gestational diabetes and fatty liver. Therefore, we investigated and compared the effects of LP or FR intake on hepatic steatosis and insulin resistance in unmated controls (CTs) and pregnant and lactating rats. Sprague-Dawley rats were fed a CT, or a 63% FR, or an 8% LP diet. Glucose tolerance test at day 17 of the study revealed greater (P < .05) blood glucose at 10 (75.6 mg/dL vs 64.0 ± 4.8 mg/dL) minutes and 20 (72.4 mg/dL vs 58.6 ± 4.0 mg/dL) minutes after glucose dose and greater area under the curve (4302.3 mg?dL^− 1? min^− 1 vs 3763.4 ± 263.6 mg?dL^− 1? min^− 1) for FR-fed dams compared with CT-fed dams. The rats were euthanized at 21 days postpartum. Both the FR- and LP-fed dams had enlarged (P < .05) livers (9.3%, 7.1% body weight vs 4.8% ± 0.2% body weight) and elevated (P < .05) liver triacylglycerol (216.0, 130.0 mg/g vs 19.9 ± 12.6 mg/g liver weight) compared with CT-fed dams. Fructose induced fatty liver and glucose intolerance in pregnant and lactating rats, but not unmated CT rats. The data demonstrate a unique physiological status response to diet resulting in the development of gestational diabetes coupled with hepatic steatosis in FR-fed dams, which is more severe than an LP diet.     

Maternal smoking during pregnancy and intellectual performance in young adult Swedish male offspring

Lundberg F, Cnattingius S, D'Onofrio B, Altman D, Lambe M, Hultman C, Iliadou A. Maternal smoking during pregnancy and intellectual performance in young adult Swedish male offspring. Paediatric and Perinatal Epidemiology 2010; 24: 79–87.
Smoking during pregnancy has been linked to an increased risk of several adverse birth outcomes. Associations with deficits in cognitive development have also been suggested. It is unclear whether these associations are due to genetic and/or environmental confounding. In a population-based Swedish cohort study on 205 777 singleton males born to Nordic mothers between 1983 and 1988, we examined the association between maternal smoking during pregnancy and the risk of poor intellectual performance in young adult male offspring.
In the cohort analyses, the risk of poor intellectual performance was increased in sons of smoking mothers compared with sons of non-smokers. Stratifying for maternal smoking habits across two pregnancies, there was an increased risk of poor intellectual performance for both sons if the mother was only smoking in the first pregnancy, but in neither son if the mother was only smoking in the second pregnancy. The effect of smoking during pregnancy on intellectual performance was not present when the association was evaluated within sibling pairs. Thus, the association between prenatal smoking exposure and offspring risk of low intellectual performance appears to be completely confounded by familial (genetic and early environmental) factors.     

孕乳期补充维生素D对仔鼠免疫球蛋白及T细胞的影响

目的探讨孕乳期补充维生素D(Vit D)对仔鼠免疫球蛋白及T细胞的影响。方法选取雌性SD大鼠24只,随机分为低、中、高剂量1,25-(OH)_2D_3组和对照组。受孕第17天起,用1 ml/kg~(-1)·d~(-1)灌胃,分别给予花生油稀释的1,25-(OH)_2D_3滴剂40、80、120 IU·ml~(-1)·kg~(-1)及等剂量花生油,至子代大鼠21 d断乳。每组随机选择6只(雌雄各半),测定22 d仔鼠血清1,25-(OH)_2D_3含量,血清免疫球蛋白A(IgA)、血清免疫球蛋白M(Ig M)、血清免疫球蛋白G(IgG)水平及CD_4~+、CD_8~+T淋巴细胞比例和CD_4~+/CD_8~+比值。结果 3组血清1,25-(OH)_2D_3含量均有所升高,中、高剂量组升高显著,差异有统计学意义(P0.05),但组间比较差异无统计学意义(P0.05);低、中剂量组仔鼠IgG含量明显升高(P0.05),高剂量组变化差异无统计学意义(P0.05),3组IgA及Ig M含量比较差异无统计学意义(P0.05);3组CD_4~+T淋巴细胞比例升高,低、中剂量组比较差异有统计学意义(P0.05),但组间比较差异无统计学意义(P0.05);3组CD_8~+T淋巴细胞比例升高,但差异无统计学意义(P0.05);3组CD_4~+/CD_8~+比值均有所升高(P0.05),且中、高剂量组CD_4~+/CD_8~+比值更高(P0.01),组间比较差异无统计学意义(P0.05),但中剂量组均数更高。结论孕乳期补充Vit D有利于增强子代的细胞免疫功能,80 IU/d剂量(相当于成人800 ng/d)较为适宜,对体液免疫功能的影响需进一步探究。     

Intake of fatty acids in western Europe with emphasis on trans fatty acids: the TRANSFAIR Study

OBJECTIVE: To assess the intake of trans fatty acids (TFA) and other fatty acids in 14 Western European countries. DESIGN AND SUBJECTS: A maximum of 100 foods per country were sampled and centrally analysed. Each country calculated the intake of individual trans and other fatty acids, clusters of fatty acids and total fat in adults and/or the total population using the best available national food consumption data set. RESULTS: A wide variation was observed in the intake of total fat and (clusters) of fatty acids in absolute amounts. The variation in proportion of energy derived from total fat and from clusters of fatty acids was less. Only in Finland, Italy, Norway and Portugal total fat did provide on average less than 35% of energy intake. Saturated fatty acids (SFA) provided on average between 10% and 19% of total energy intake, with the lowest contribution in most Mediterranean countries. TFA intake ranged from 0.5% (Greece, Italy) to 2.1% (Iceland) of energy intake among men and from 0.8% (Greece) to 1.9% among women (Iceland) (1.2-6.7 g/d and 1.7-4.1 g/d, respectively). The TFA intake was lowest in Mediterranean countries (0.5-0.8 en%) but was also below 1% of energy in Finland and Germany. Moderate intakes were seen in Belgium, The Netherlands, Norway and UK and highest intake in Iceland. Trans isomers of C18:1 were the most TFA in the diet. Monounsaturated fatty acids contributed 9-12% of mean daily energy intake (except for Greece, nearly 18%) and polyunsaturated fatty acids 3-7%. CONCLUSION: The current intake of TFA in most Western European countries does not appear to be a reason for major concern. In several countries a considerable proportion of energy was derived from SFA. It would therefore be prudent to reduce intake of all cholesterol-raising fatty acids, TFA included.     

Mild maternal iron deficiency anemia during pregnancy and lactation in guinea pigs causes abnormal auditory function in the offspring

Iron deficiency (ID) anemia (IDA) adversely affects different aspects of the nervous system such as myelinogenesis, neurotransmitters synthesis, brain myelin composition, and brain fatty acid and eicosanoid metabolism. Infant neurophysiological outcome in response to maternal IDA is underexplored, especially mild to moderate maternal IDA. Furthermore, most human research has focused on childhood ID rather than prenatal or neonatal ID. Thus, our study evaluated the consequences of mild maternal IDA during pregnancy and lactation on the offsprings' auditory function using the auditory brainstem response (ABR). This technique provides objective measures of auditory acuity, neural transmission times along the peripheral and brainstem portions of the auditory pathway, and postnatal brain maturation. Female guinea pigs (n = 10/group) were fed an iron sufficient diet (ISD) or an iron deficient diet (IDD) (144 and 11.7 mg iron/kg) during their acclimation, gestation, and lactation periods. From postnatal d (PNd) 9 onward, the ISD was given to all weaned offspring. ABR were collected from the offspring on PNd24 using a broad range of stimulus intensities in response to 2, 4, 8, 16, and 32 kHz tone pips. IDA siblings (n = 4), [corrected] compared with the IS siblings (n = 5), had significantly elevated ABR thresholds (hearing loss) in response to all tone pips. These physiological disturbances were primarily due to a sensorineural hearing loss, as revealed by the ABR's latency-intensity curves. These results indicate that mild maternal IDA during gestation and lactation altered the hearing and nervous system development of the young offspring.     

Effect of maternal iron restriction during pregnancy on renal morphology in the adult rat offspring

In rats, maternal anaemia during pregnancy causes hypertension in the adult offspring, although the mechanism is unknown. The present study investigated the renal morphology of adult rats born to mothers who were Fe-deficient during pregnancy. Rats were fed either a control (153 mg Fe/kg diet, n 7) or low-Fe (3 mg/kg diet, n 6) diet from 1 week before mating and throughout gestation. At delivery, the Fe-restricted (IR) mothers were anaemic; the IR pups were also anaemic and growth-retarded at 2 d of age. At 3 and 16 months, systolic blood pressure in the IR offspring (163 (sem 4) and 151 (sem 4) mmHg respectively, n 13) was greater than in control animals (145 (sem 3) and 119 (sem 4) mmHg respectively, n 15, P<0.05). At post mortem at 18 months, there was no difference in kidney weight between treatment groups, although relative kidney weight as a fraction of body weight in the IR offspring was greater than in control animals (P<0.05). Glomerular number was lower in the IR offspring (11.4 (sem 1.1) per 4 mm(2), n 13) compared with control rats (14.8 (sem 0.7), n 15, P<0.05). Maternal treatment had no effect on glomerular size, but overall, female rats had smaller and more numerous glomeruli per unit area than male rats. When all animals were considered, inverse relationships were observed between glomerular number and glomerular size (r-0.73, n 28, P<0.05), and glomerular number and systolic blood pressure at both 3 months (r-0.42, n 28, P<0.05) and 16 months of age (r-0.64, n 28, P<0.05). Therefore, in rats, maternal Fe restriction causes hypertension in the adult offspring that may be due, in part, to a deficit in nephron number.