Cancer cachexia and tumor growth reduction in Walker 256 tumor-bearing rats supplemented with N-3 polyunsaturated fatty acids for one generation

In this study we investigated the effect of lifelong supplementation of the diet with coconut oil (CO, rich in saturated fatty acids) or fish oil (FO, rich in n-3 polyunsaturated fatty acids, PUFAs) on tumor growth, animal survival, and metabolic indicators of cachexia in adult rats. Female Wistar rats were supplemented with CO or FO prior to mating and then throughout pregnancy and gestation, and then the male offspring were supplemented from weaning until 90 days of age. Then they were inoculated subcutaneously with Walker 256 tumor cells. Tumor weight at 14 days in control rats (those fed standard chow) was approximately 20 g. These animals displayed cancer cachexia, which was characterized by loss of weight, hypoglycemia, hyperlacticidemia, hypertriacylglycerolemia, and depletion of glycogen stores. Supplementation of the diet with CO did not change these parameters, except that there was a smaller decrease in serum triacylglycerol concentration. Supplementation of the diet with FO significantly decreased tumor growth (by approximately 60%), increased survival (50% at 30 days postinoculation vs. 30% in the controls and 13.5% in the CO group), and prevented the fall in body weight. Furthermore, FO supplementation partly abolished the fall in serum glucose, totally prevented the elevation in serum lactate concentrations, partly prevented the hypertriacylgylcerolemia, and preserved tissue glycogen stores. Lifelong consumption of FO, rich in n-3 PUFAs, protects against tumor growth and cancer cachexia and improves survival.     

Maternal protein restriction during pregnancy and lactation in rats imprints long-term reduction in hepatic lipid content selectively in the male offspring

Maternal protein restriction during pregnancy and lactation reduces whole body lipid stores and alters lipid homeostasis in the adult offspring. Lipid homeostasis in the body is regulated, in part, by the liver via the metabolic processes of synthesis and utilization of lipids. The present study tested the hypothesis that maternal protein restriction will imprint changes in hepatic lipid metabolism and thereby alter the hepatic lipid content of the adult offspring. Pregnant rats were fed purified diets containing 19% protein (control group) or 8% protein (low-protein group) throughout pregnancy and lactation. On day 28, pups from both groups were weaned onto regular laboratory chow. On days 65 and 150, male and female pups from each litter in both groups were killed and blood and liver collected. Maternal protein restriction was found to reduce birth weight and produce long-term reduction in the body weight of the offspring. On day 65, liver triglyceride content was decreased by 40% in the male offspring that were fed a low-protein diet. The reduction in liver triglyceride content persisted until day 150, at which time it was accompanied by decreases in hepatic cholesterol content. No such changes were observed in the female offspring. To determine if the alterations in liver lipid content resulted in compensatory changes in liver carbohydrate stores, hepatic glycogen content was measured in male offspring. Hepatic glycogen content was similar between the 2 groups on days 65 and 150. In conclusion, the present study in rats showed that maternal protein restriction during pregnancy and lactation imprints long-term changes in hepatic lipid content selectively in the male offspring.     

A maternal 'junk food' diet in pregnancy and lactation promotes an exacerbated taste for 'junk food' and a greater propensity for obesity in rat offspring

Obesity is generally associated with high intake of junk foods rich in energy, fat, sugar and salt combined with a dysfunctional control of appetite and lack of exercise. There is some evidence to suggest that appetite and body mass can be influenced by maternal food intake during the fetal and suckling life of an individual. However, the influence of a maternal junk food diet during pregnancy and lactation on the feeding behaviour and weight gain of the offspring remains largely uncharacterised. In this study, six groups of rats were fed either rodent chow alone or with a junk food diet during gestation, lactation and/or post-weaning. The daily food intakes and body mass were measured in forty-two pregnant and lactating mothers as well as in 216 offspring from weaning up to 10 weeks of age. Results showed that 10 week-old rats born to mothers fed the junk food diet during gestation and lactation developed an exacerbated preference for fatty, sugary and salty foods at the expense of protein-rich foods when compared with offspring fed a balanced chow diet prior to weaning or during lactation alone. Male and female offspring exposed to the junk food diet throughout the study also exhibited increased body weight and BMI compared with all other offspring. This study shows that a maternal junk food diet during pregnancy and lactation may be an important contributing factor in the development of obesity.     

孕期补充二十二碳六烯酸对子代大鼠脂肪代谢及解偶联蛋白2基因表达的影响

目的探讨孕期补充二十二碳六烯酸(DHA)对子代脂肪代谢和解偶联蛋白2基因表达的影响。方法将SD雌鼠按体重随机分成A、B、C三组,孕期分别食用基础膳食(A)、补充低剂量DHA膳食(B)、补充高剂量DHA膳食(C)。所产雄性仔鼠均由A组母鼠哺乳,21d断乳,用基础膳食喂饲至出生后的第8w。将A组仔鼠按体重随机分为正常对照组A1、高脂对照组A2,A1组继续食用基础膳食至实验结束,A2、B、C三组给予高脂膳食喂饲7w,结束实验。在第8w、15w时各组随机选取8只仔鼠处死,观察体重、体脂含量、血脂和白色脂肪UCP2mRNA表达丰度变化。结果各组仔鼠出生体重和出生后第8w体重均无差异(P0.05)。第8w时B、C组仔鼠体脂含量、血清甘油三酯水平显著低于对照组(P0.05);第15w时,A2组体重、体脂含量、甘油三酯均显著高于A1组(P0.05),B、C两组体重和血清甘油三酯水平显著低于A2组(P0.05)。第8w时,B、C两组大鼠白色脂肪组织UCP2mRNA水平均高于A组;15w时,UCP2mRNA水平依次为C组高于B组、A1和A2组,A2组最低。结论孕期适量DHA补充可降低子代大鼠摄取高脂肪膳食时的体重、血清甘油三酯,即降低肥胖发生风险,改善脂肪代谢;其中对子代白色脂肪组织UCP2基因表达的上调作用可能是其潜在机制之一。     

孕鼠补充二十二碳六烯酸对仔鼠肝脏肉碱棕榈酰转移酶-I mRNA表达的影响

目的 研究孕鼠补充二十二碳六稀酸(DHA)对仔鼠脂肪代谢及肉碱棕榈酰转移酶-I(CPT-I)mRNA水平的影响.方法 成年SD雌鼠随机分成A、B、C三组,待其妊娠后A组给予基础饲料、B组补充低剂量的DHA(1g/kg bw),C组补充高剂量的DHA(2g/kg bw).所有雄性仔鼠出生后均由A组母鼠哺乳,断乳后给予基础饲料喂饲至出生后第8周.每组8只,动态观察仔鼠的体重、体脂含量、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白(HDL-C)7L CPT-I mRNA水平.结果 三组仔鼠的出生体重差异无显著性(P>0.05);仔鼠出生后的第8周时,C组的体重显著低于A组(P<0.05),B、C组的体脂含量、TG水平显著低于A组(P<0.05).而C组HDL-C水平显著高于A组(P<0.05),但三组TC水平差异无显著性(P>0.05).动态观察表明,肝脏CPT-I mRNA水平持续性出现B、C高于A组,C组高于B组.结论 孕期补充DHA可能通过持续性上调仔鼠肝脏CPT-I基因表达来增强脂肪酸的氧化,降低血脂水平,但孕期摄入过量的DHA可能对子代产生不利影响.     

Differential effects of fish oil and folic acid supplementation during pregnancy in rats on cognitive performance and serum glucose in their offspring

OBJECTIVE: We studied the effect of folic acid and polyunsaturated fatty acid supplementation during pregnancy in Wistar albino rats on cognitive performance and serum glucose concentrations in their pups. METHODS: Pregnant female rats from four groups (n = 6/group) were fed casein diets with 18% protein and 2 mg of folic acid/kg of diet (group I), 12% protein and no folic acid (group II), 12% protein and 8 mg of folic acid/kg of diet (group III), or 12% protein and 70 g of cod liver oil/kg of diet (group IV). All pups were weaned on standard control diet with 18% protein. Cognitive performance, brain fatty acid profile, and serum glucose concentrations were studied in offspring at age 6 mo. RESULTS: There was no significant difference in length of gestation or litter size, but the litter weight for group IV was lower (P = 0.047) than that for group I. After weaning, males in group II had lower (P < 0.05) body weights, but those in group III had weights comparable to those in group I for both sexes. In group IV, body weights were lower beyond 15 wk (P < 0.05). Relative brain weight and cognitive performance were significantly higher (P < 0.05) in group IV males and showed higher levels of brain gamma-linolenic acid. Further, these animals had serum glucose levels comparable to those of control animals at age 6 mo, whereas serum glucose levels were higher in males from groups II (P = 0.01) and III (P = 0.01). CONCLUSION: Fish oil supplementation during pregnancy improved cognitive performance and maintained glucose levels into adulthood, unlike folic acid supplementation, which supported only fetal growth and did not maintain glucose levels.     

Glucose intolerance associated with early-life exposure to maternal cafeteria feeding is dependent upon post-weaning diet

In addition to being a risk factor for adverse outcomes of pregnancy, maternal obesity may play a role in determining the long-term disease patterns observed in the resulting offspring, with metabolic and dietary factors directly programming fetal development. The present study evaluated the potential for feeding rats an obesogenic cafeteria diet (O) pre-pregnancy, during pregnancy, during lactation and for the offspring post-weaning, to programme glucose tolerance. Early-life exposure to an O diet had no significant effect on offspring food intake. Early-life programming associated with O feeding to induce maternal obesity was associated with reduced adiposity in offspring weaned onto low-fat chow. Adult offspring exposed to an O diet in early life and weaned on a chow diet had low fasting glucose and insulin concentrations and appeared to be more sensitive to insulin during an intraperitoneal glucose tolerance test. When weaned on an O diet, male offspring were more prone to glucose intolerance than females. On the basis of the area under the glucose curve, maternal O feeding at any point from pre-mating to lactation was associated with impaired glucose tolerance. The mechanism for this was not identified, although increased hepatic expression of Akt2 may have indicated disturbance of insulin signalling pathways. The observations in the present study confirm that maternal overnutrition and obesity during pregnancy are risk factors for metabolic disturbance in the resulting offspring. Although the effects on glucose homeostasis were independent of offspring adiposity, the programming of a glucose-intolerant phenotype was only observed when offspring were weaned on a diet that induced greater fat deposition.     

Prenatal programming of angiotensin II type 2 receptor expression in the rat

Exposure to undernutrition during fetal life has been proposed as an underlying cause of adult hypertension. Epidemiological studies demonstrating relationships between low birth weight and later CVD are supported by animal experiments indicating that manipulations of the maternal diet in pregnancy exert programming effects upon blood pressure control. Pregnant female Wistar rats were fed a control diet (n 13) or a low-protein diet (n 12) throughout pregnancy. At delivery all animals were fed the same standard laboratory chow diet. Analysis of nephron number in kidneys obtained from 4-week-old offspring showed that this was significantly (P<0.05) reduced in animals exposed to maternal protein restriction. At this age rats exposed to low-protein diets in utero had systolic blood pressures that were significantly greater than those of control animals (+23 mmHg, P<0.05). Administration of ascending doses of angiotensin II (1-40 ng/kg body weight intravenously) to 10-week-old anaesthetised female rats showed that the pressor response to the peptide was greater and more prolonged in animals exposed to low-protein diets in utero. Renal expression of mRNA for the angiotensin II type 1A receptor was similar in the two groups of rats, but low-protein-exposed animals had significantly lower renal expression of the type 2 receptor (P=0.023). These results suggest that maternal nutritional status programmes expression of the renal angiotensin II type 2 receptor. This may play a key role in the impairment of renal development and the elevation of blood pressure noted in rats exposed to intra-uterine protein restriction.     

Long-term programming of blood pressure by maternal dietary iron restriction in the rat

We have reported that blood pressure was elevated in 3-month-old rats whose mothers were Fe-restricted during pregnancy. These animals also had improved glucose tolerance and decreased serum triacylglycerol. The aim of the present study was to determine whether these effects of maternal nutritional restriction, present in these animals at 3 months of age, can be observed in the same animals in later life. Pulmonary and serum angiotensin converting enzyme (ACE) concentrations were also measured to investigate whether the renin-angiotensin system was involved in the elevation of blood pressure observed in the offspring of Fe-restricted dams. Systolic blood pressure was higher in the offspring of Fe-restricted dams at 16 months of age. Heart and kidney weight were increased as a proportion of body weight in the offspring of Fe-restricted dams. The pulmonary ACE concentration was not significantly different between the groups. The serum ACE concentration was significantly elevated in the offspring of Fe-restricted dams at 3 but not 14 months of age. There was a strong correlation between serum ACE levels at 3 and 14 months of age. Glucose tolerance and serum insulin were not different between the maternal diet groups. Serum triacylglycerol tended to be lower in the offspring of Fe-restricted dams. There were no differences in serum non-esterified fatty acids or serum cholesterol between the maternal diet groups. This study provides further evidence that maternal nutrition has effects on the offspring that persist throughout life. At 16 months of age, the elevation of blood pressure in Fe-restricted offspring does not appear to be mediated via changes in ACE levels. Both cardiac hypertrophy and decreased serum triacylglycerol have also been observed in Fe-restricted fetuses, suggesting that these changes may be initiated in utero.     

Effect of palatable hyperlipidic diet on lipid metabolism of sedentary and exercised rats

OBJECTIVE: The present study was designed to examine 1) whether continuous feeding with a palatable hyperlipidic diet and cycling this diet with chow diet would affect lipid and carbohydrate metabolism in a similar way; and 2) whether the effect of chronic exercise on lipid and carbohydrate metabolism would be modified by these diet regimens. METHODS: Male 25-d-old Wistar rats were assigned to one of six groups: sedentary rats fed with chow diet; exercised (swimming 90 min/d, 5 d/wk) rats fed with chow diet; sedentary rats fed with a palatable hyperlipidic diet; exercised rats fed with the palatable hyperlipidic diet; sedentary rats fed with food cycles (four cycles alternating the chow and hyperlipidic diets weekly); and exercised rats fed with food cycles. After 8 wk of treatment, the animals were killed 24 h after the last exercise session. RESULTS: The hyperlipidic diet and food cycles schedules caused similar increases in body weight gain, carcass lipogenesis rate and adiposity, lipid content of the liver and gastrocnemius muscle, and serum total lipid, triacylglycerol, insulin, and leptin levels. The exercise attenuated body weight gain, adipose tissue mass, and serum triacylglycerol, insulin, and leptin levels similarly in the hyperlipidic and food cycles groups. Carcass lipogenesis rate was not affected by exercise in any of the three groups. CONCLUSIONS: The data showed that the continuous intake of a hyperlipidic palatable diet for 8 wk and the alternation of the high-fat intake with periods of chow intake cause obesity and affected lipid metabolism in a similar way. Chronic exercise attenuated body weight gain and adiposity and improved serum lipid concentrations in both high-fat feeding regimens.     

孕期补充二十二碳六烯酸对母鼠脂肪代谢及CPT-Ⅰ mRNA表达的影响

目的探讨孕期补充二十二碳六烯酸(DHA)对母鼠脂肪代谢和肉碱棕榈酰转移酶-Ⅰ(CPT-Ⅰ)mRNA表达的影响。方法将SD雌鼠按体重随机分成A、B、C3组,孕期分别食用补充高剂量DHA膳食(A)、补充低剂量DHA膳食(B)、普通膳食(C),待母鼠分娩,实验结束。观察母鼠妊娠期间体重变化及各组子鼠出生数量、出生体重情况,检测母鼠产后肾周脂肪含量、血清甘油三酯(TG)、血清总胆固醇(TC)、血清高密度脂蛋白(HDL-C)水平、瘦素(Leptin)及肝脏组织中CPT-ⅠmRNA的表达丰度。结果各组孕鼠妊娠时间、产子数量、子鼠出生体重均无明显差异,但A、B组的母鼠产后血清甘油三酯水平低于C组;A组母鼠孕期增重量、肾周脂肪含量、总胆固醇、瘦素水平均明显低于C组;A、B组母鼠产后肝脏组织的CPT-ⅠmRNA水平高于C组。结论孕期补充DHA有调节母体血脂、减少体内脂肪含量的作用,而CPT-Ⅰ基因表达的上调可能是其一潜在机制。     

In utero exposure to maternal low protein diets induces hypertension in weanling rats, independently of maternal blood pressure changes

The association between maternal nutrition, fetal growth and the later development of hypertension was investigated in the rat. Animals were habituated to diets containing 18% (control) or 9% (low) protein by weight. The rats were mated and maintained on the diets until the end of pregnancy. Lactating dams were transferred onto standard chow diet. Systolic blood pressure was determined in male and female weanling offspring, using an indirect tail-cuff method. To assess the direct effects of low protein diets upon blood pressure of adult animals, a group of male and female rats were fed 18% or 9% protein for 14 days. Blood pressure was determined at the beginning and end of the feeding period. Blood pressure was additionally assessed over 14 days in pregnant rats fed control or low protein diets. Low protein diets did not alter systolic blood pressure in adult male or female rats. The blood pressures of pregnant females fed 18% or 9% protein diets did not significantly differ at any stage of pregnancy. Rats fed 9% protein diets gave birth to significantly smaller pups. Litter sizes were unaltered, and no differences in perinatal mortality were observed. Pups exposed to maternal low protein in utero had higher systolic blood pressure at the age of 4 weeks, when compared to control pups. The phenomenon was observed in both male and female offspring. Blood pressures at 4 weeks of age were strongly associated with maternal protein intake (r = -0.55). Associations were also noted between blood pressure and maternal weight at mating (r = 0.48), and weight gain in pregnancy (r = -0.30). Fetal exposure to maternal low protein diets induces hypertension in rats. The phenomenon is observed early in life and is independent of sex and the influence of maternal blood pressure. The low protein diet itself did not produce an increase in the blood pressure of adult rats.     

The effect of glutamine and dihydroxyacetone supplementation on food intake, weight gain, and postprandial glycogen synthesis in female Zucker rats

OBJECTIVE: We sought to test the hypothesis that increasing postprandial hepatic glycogen synthesis rate would decrease food intake and growth rate in obese Zucker rats. DESIGN: Supplements of glutamine, with and without dihydroxyacetone (DHA), which have previously been shown to stimulate hepatic glycogen synthesis, were administered in the diet of obese Zucker rats for periods of 1 and 3 wk. MEASUREMENTS: Food intake and body weight were monitored throughout the experiments. At the end of the feeding period the rats were fed a test meal and injected with (3)H(2)O to measure in vivo rates of glycogen and lipid synthesis. Final plasma glucose and triacylglycerol and hepatic glycogen content were also determined. Carcass fat and water contents were also measured in the 3-wk study. RESULTS: Dietary glutamine had no effect on food intake, weight gain, or body composition. Addition of DHA caused a reduction in food intake and weight gain and a stimulation of in vivo hepatic glycogen synthesis after 1 wk, but these changes were abolished by the end of 3 wk. Hepatic lipogenesis in vivo was increased by DHA treatment for 1 and 3 wk. CONCLUSIONS: Stimulation of hepatic glycogen synthesis by DHA treatment was associated with a reduction in food intake. However, the effect of DHA on glycogen synthesis and food intake disappeared after 3 wk of supplementation.     

Low arachidonic acid rather than alpha-tocopherol is responsible for the delayed postnatal development in offspring of rats fed fish oil instead of olive oil during pregnancy and lactation

This study was designed to compare in rats the effects of dietary fish oil and olive oil during pregnancy and lactation on offspring development, fatty acid profile and vitamin E concentration. From d 0 of pregnancy, female Sprague-Dawley rats were divided into two groups that were fed purified diets that differed only in their nonvitamin lipid components. One diet contained 10 g fish oil/100 g diet (FOD), whereas the other contained 10 g olive oil/100 g diet (OOD). At d 20 of gestation, maternal adipose tissue fatty acid profile did not differ between rats fed the two diets, whereas both maternal and fetal plasma and liver arachidonic acid (AA) contents were proportionally lower and eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid contents were higher in the FOD group than in the OOD group. alpha-Tocopherol concentration was lower in maternal and fetal plasma, liver and brain in the FOD group than in the OOD group. The postnatal increase in body weight and length was less and body and psychomotor maturation indices were delayed in pups from FOD-fed dams compared with those from OOD-fed dams. This difference was maintained when pups were cross-fostered at birth, with the delay in postnatal development present in the pups suckling dams fed FOD during lactation. At age 21 d, pups suckling dams fed FOD had lower AA and higher EPA and DHA concentrations in brain phospholipids. Although alpha-tocopherol in plasma and liver was lower in pups suckling dams fed FOD rather than OOD, brain alpha-tocopherol concentrations did not differ. Milk yield and milk alpha-tocopherol and AA concentrations were lower and EPA and DHA were higher in the milk of dams fed FOD compared with those fed OOD. Postnatal development indices and the proportion of plasma, liver and brain AA concentrations, although not plasma, liver and brain alpha-tocopherol concentrations, recovered to the values found in dams fed OOD when the FOD was supplemented with gamma-linolenic acid. However, postnatal development indices were not recovered when the FOD was supplemented with sufficient exogenous vitamin E to increase plasma and liver alpha-tocopherol concentrations above those in dams fed OOD. Thus, although feeding FOD during pregnancy and lactation decreases both alpha-tocopherol and AA concentrations, the latter deficiency rather than the former seems to be responsible for delayed postnatal development of rat pups.     

孕哺期高脂膳食对子代SD大鼠血尿酸水平的影响

目的 探索孕哺期高脂膳食对子代SD大鼠血尿酸的影响。方法 10只成年雌性SD孕鼠随机分为对照组和高脂组,分别饲以标准鼠粮和含20%猪油的高脂饲料。4周龄断乳后,对照组雄性仔鼠中10只维持标准鼠粮(B/B),10只转饲以高脂饲料(B/HF);高脂组雄性仔鼠中10只维持原饲料(HF/HF),10只转饲以标准鼠粮(HF/B)。至12周龄,称量体重,测定血尿酸水平及黄嘌呤氧化酶和腺苷脱氨酶活性。结果 HF/HF组仔鼠体重、血尿酸水平及黄嘌呤氧化酶(xanthine oxidase,XOD)活性均显著高于B/B组及HF/B组(P＜0.05),HF/B组仔鼠血尿酸水平及XOD活性高于B/B组(P＜0.05),血ADA活性各组间差异无统计学意义(P>0.05)。结论 孕哺期高脂膳食可对子代高尿酸血症的发生产生影响,断乳后膳食调整可减弱其影响,机制可能与血黄嘌呤氧化酶活性的改变有关。     

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.     

孕期高中链脂肪膳食对后代UCP3基因的影响

目的:探讨孕期膳食对子代肥胖和肥胖相关基因解偶联蛋白3(UCP3)表达的影响,寻找肥胖预防和治疗的靶标。方法:W istar孕鼠分别食用标准膳食和高中链脂肪膳食,所产雄性子鼠分别为对照组和高中链脂肪酸组(HMCFA),3周断乳后大鼠均食用标准膳食至成年,将对照组的大鼠随机分为两组:一组继续食用标准膳食;另一组为高脂对照组(HFCON),HFCON和HMCFA组的大鼠均高脂膳食诱导肥胖6周。分别在大鼠出生、断乳、成年、高脂诱导肥胖后各处死一批大鼠,取褐色脂肪检测UCP3 mRNA的表达。结果:与孕期标准膳食的子代相比,孕期高中链脂肪膳食可持续降低子代大鼠的体重和肥胖率(P<0.05),同时也可持续升高UCP3 mRNA的表达。结论:孕期高中链脂肪膳食可降低子代成年高脂诱导肥胖的发生;其机制为通过程序性升高子代UCP3基因的表达增加脂肪氧化和热能散失。     

Maternal fish oil supplementation ameliorates maternal high-fructose diet-induced dyslipidemia in neonatal mice with suppression of lipogenic gene expression in livers of postpartum mice

Maternal fructose consumption during pregnancy and lactation is associated with metabolic dysregulation in offspring. We tested the hypothesis that fish oil (FO) supplementation during pregnancy and lactation improves fructose-induced metabolic dysregulation in postpartum dams and offspring mice. We therefore aimed to determine the effects of FO supplementation on metabolic disruption in neonatal mice and dams induced by a maternal high-fructose diet (HFrD). The weight of the offspring of dams fed with HFrD on postnatal day 5 was significantly low, but this was reversed by adding FO to the maternal diet. Feeding dams with HFrD significantly increased plasma concentrations of triglycerides, uric acid, and total cholesterol, and decreased free fatty acid concentrations in offspring. Maternal supplementation with FO significantly suppressed HFrD-induced hypertriglyceridemia and hyperuricemia in the offspring. Maternal HFrD induced remarkable mRNA expression of the lipogenic genes Srebf1, Fasn, Acc1, Scd1, and Acly in the postpartum mouse liver without affecting hepatic and plasma lipid levels. Although expression levels of lipogenic genes were higher in the livers of postpartum dams than in those of nonmated mice, HFrD feeding increased the hepatic lipid accumulation in nonmated mice but not in postpartum dams. These findings suggest that although hepatic lipogenic activity is higher in postpartum dams than nonmated mice, the lipid consumption is enhanced in postpartum dams during pregnancy and lactation. Maternal FO supplementation obviously suppressed the expression of these lipogenic genes. These findings coincide with reduced plasma triglyceride concentrations in the offspring. Therefore, dietary FO apparently ameliorated maternal HFrD-induced dyslipidemia in offspring by suppressing maternal lipogenic gene expression and/or neonatal plasma levels of uric acid.     

Docosahexaenoic acid supplementation during pregnancy as phospholipids did not improve the incorporation of this fatty acid into rat fetal brain compared with the triglyceride form

Prenatal docosahexaenoic acid (DHA) supply is important to ensure an adequate infant neurodevelopment. Several fat supplements with DHA under different chemical structures are available. There is an increased placental phospholipase activity at the end of pregnancy. The hypothesis of this study was to discern whether DHA consumption during pregnancy as phospholipids (PLs) could be more available for placental DHA uptake and fetal accretion than triglycerides (TGs) form. We aimed to evaluate maternofetal DHA status in pregnant rats fed with DHA as PL from egg yolk or TG from algae oil to determine which source might be most effective during pregnancy. Three experimental diets were tested: 2.5% DHA-TG (n = 10), 2.5% DHA-PL (n = 9), and 9% DHA-PL (n = 9). The total PL content of these diets was 2%, 12%, and 38%, respectively. We determined dietary fat absorption and quantified fatty acids by gas chromatography in maternal and fetal tissues. Dietary PL enhanced significantly dietary fat absorption. However, animals fed the highest PL-content diet (38% PL and 9% DHA-PL) stored most of the absorbed fat in maternal liver, promoting hepatic steatosis, which was not observed in the lower PL-content diets (12% and 2%). Despite higher fat absorption of PL-containing diets, maternal and fetal tissues (including fetal brain) did not show major differences in DHA content between the 2.5% DHA-PL and 2.5% DHA-TG–fed groups. We conclude that the chemical form of DHA consumed by the rat during gestation (PL or TG) does not differentially affect DHA accretion into fetal brain, and both lipid sources can be equally used for maternal DHA supplementation during pregnancy.     

孕乳期补充鱼油对大鼠行为发育的影响

目的探讨孕、乳期补充富含DHA鱼油对大鼠行为发育的影响.方法以出生前、后脑发育关键期大鼠为研究对象,设1个对照组和添加鱼油的3个剂量组(其中DHA的量分别为0、7.5、15.0、30.0 g/kg饲料),喂养期限为孕0日至仔鼠45日龄.观察妊娠、分娩一般指标,进行断乳前行为发育评价、幼鼠学习行为测试等.结果与对照组相比,DHA 15.0 g/kg饲料组新生鼠脑重显著增加(P＜0.05);2项新生反射指标平面翻正、视觉定向发育显著提前(P＜0.05);跳台潜伏期延长,错误次数减少和避暗潜伏期延长(P＜0.05).结论孕、乳期补充一定剂量的DHA,可对子代大鼠神经发育产生有益影响;孕、乳期补充DHA的较适剂量为15.0 g/kg饲料.