Oxidized fat reduces milk triacylglycerol concentrations by inhibiting gene expression of lipoprotein lipase and fatty acid transporters in the mammary gland of rats

Feeding oxidized fats to lactating rats causes a strong reduction of triacylglycerol concentration in the milk. The reason for this, however, has not yet been elucidated. Pregnant Sprague-Dawley rats were assigned to 2 groups of 11 rats each and fed diets containing either fresh fat (FF group) or an oxidized fat (OF group) from d 1 to d 20 of lactation. Concentrations of triacylglycerols and long-chain fatty acids in the milk and weight gain of suckling pups were lower in the OF group than in the FF group (P < 0.05). Concentrations of medium-chain fatty acids in the milk and messenger RNA (mRNA) abundance of lipogenic enzymes in the mammary gland did not differ between the 2 groups of rats. However, the OF group had a lower concentration of triacylglycerols and nonesterified fatty acids (NEFA) in plasma and lower mRNA concentrations of lipoprotein lipase and fatty acid transporters in the mammary gland than the FF group (P < 0.05). Moreover, the OF group had higher mRNA concentrations of hepatic lipase, fatty acid transporters, and several genes involved in fatty acid oxidation in the liver than the FF group (P < 0.05). The present findings suggest that a dietary oxidized fat lowers the concentration of triacylglycerols in the milk by a reduced uptake of fatty acids from triacylglycerol rich-lipoproteins and NEFA into the mammary gland. The study, moreover, indicates that an oxidized fat impairs normal metabolic adaptations during lactation, which promote the utilization of metabolic substrates by the mammary gland for the synthesis of milk.     

A high dietary lipid intake during pregnancy and lactation enhances mammary gland lipid uptake and lipoprotein lipase activity in rats.

Rats fed a diet with high fat concentration produce larger amounts of milk with a higher lipid concentration than rats fed a lower fat diet. This investigation was designed to study the relationship between dietary fat intake, mammary gland lipid uptake and lipogenesis in rat dams fed, during pregnancy and lactation, one of two purified diets, with equal energy density, containing 2.5 (LL) or 20 g fat/100 g diet (HL). Milk lipid concentration and fatty acid composition were determined at d 14 of lactation. Mammary gland lipogenesis, lipoprotein lipase (LPL) activity and the uptake of [1-(14)C]triolein by the mammary gland and its transfer to the pups was measured. The intestinal absorption of oral (14)C-lipid, (14)CO(2) production and the amount of (14)C-lipid transferred to the pups (milk clot + pups carcass) were significantly higher in the HL group than in the LL group (P < 0.05). Mammary gland lipogenesis was 75% lower and LPL activity was 30% higher in the HL group (P < 0.05). Medium-chain fatty acids (C6-C14) excretion was 46% lower and that of long-chain fatty acids was 142% (P < 0.001) higher in the HL group than in the LL group. The higher milk lipid excretion in the rats fed a high-fat diet resulted from a larger uptake of dietary lipid by the mammary gland, indicated by a larger transfer of (14)C-lipid to the pups and by a higher LPL activity in the mammary gland.     

Dietary oxidized fat prevents ethanol-induced triacylglycerol accumulation and increases expression of PPARalpha target genes in rat liver

Alcoholic fatty liver results from an impaired fatty acid catabolism due to blockade of PPARalpha and increased lipogenesis due to activation of sterol regulatory element-binding protein (SREBP)-1c. Because both oxidized fats (OF) and conjugated linoleic acids (CLA) have been demonstrated in rats to activate hepatic PPARalpha, we tested the hypothesis that these fats are able to prevent ethanol-induced triacylglycerol accumulation in the liver by upregulation of PPARalpha-responsive genes. Forty-eight male rats were assigned to 6 groups and fed isocaloric liquid diets containing either sunflower oil (SFO) as a control fat, OF prepared by heating of SFO, or CLA, in the presence and absence of ethanol, for 4 wk. Administration of ethanol lowered mRNA concentrations of PPARalpha and the PPARalpha-responsive genes medium chain acyl-CoA dehydrogenase, long chain acyl-CoA dehydrogenase, acyl-CoA oxidase, carnitine palmitoyl-CoA transferase I, and cytochrome P450 4A1 and increased triacylglycerol concentrations in the liver (P < 0.05). OF increased hepatic mRNA concentrations of PPARalpha-responsive genes and lowered hepatic triacylglycerol concentrations compared with SFO (P < 0.05) whereas CLA did not. Rats fed OF with ethanol had similar mRNA concentrations of PPARalpha-responsive genes and similar triacylglycerol concentrations in the liver as rats fed SFO or CLA without ethanol. In contrast, hepatic mRNA concentrations of SREBP-1c and fatty acid synthase were not altered by OF or CLA compared with SFO. This study shows that OF prevents an alcohol-induced triacylglycerol accumulation in rats possibly by upregulation of hepatic PPARalpha-responsive genes involved in oxidation of fatty acids, whereas CLA does not exert such an effect.     

A thermally oxidized dietary oil does not lower the activities of lipogenic enzymes in mammary glands of lactating rats but reduces the milk triglyceride concentration

It was shown that dietary thermoxidized oils suppress gene expression of lipogenic enzymes in the liver. This study was performed to investigate whether oxidized oils also influence the activities of lipogenic enzymes in the mammary gland of lactating rats. Female rats (n = 24) were divided into two groups at 4 wk of age. They were fed for 14 wk diets with either fresh oil (a mixture of sunflower oil, linseed oil, and palm oil, 73:15:12) or oxidized oil (a mixture of sunflower oil and linseed oil, 80:20) prepared by heating at a temperature of 50 degrees C for 16 d. At the age of 12 wk, the rats were mated. At birth, litters were adjusted to 7 pups/dam. Milk was sampled at d 14 of lactation; mammary glands were taken at d 19 of lactation. Rats fed the oxidized oil had a lower activity of glucose-6-phosphate dehydrogenase (G6PDH) in their mammary glands than those fed the fresh oil (P < 0.05); the activities of fatty acid synthase (FAS) and acetyl-CoA-carboxylase in mammary glands did not differ. Relative mRNA concentrations of G6PDH, FAS, and sterol-regulatory element binding protein-1, a regulator of lipogenesis, in the mammary gland did not differ between groups. The concentrations in the milk of medium-chain fatty acids (C8-C14), the major products of fatty acid synthesis in mammary glands, also did not differ. The concentrations of triglycerides and long-chain fatty acids (C18-C22), however, were lower in the milk of rats fed the oxidized oil than in the milk of rats fed the fresh oil (P < 0.05). In conclusion, this study shows that feeding oxidized oils to lactating rats does not affect lipogenic enzymes in mammary glands but reduces the triglyceride concentrations in their milk.     

Low intensity exercise and varying proportions of dietary glucose and fat modify milk and mammary gland compositions and pup growth.

Exercise during pregnancy or lactation may create a competition for glucose between the exercising muscle and either the developing fetus or the lactating mammary gland. To test these two hypotheses, pregnant rats were randomly assigned to isoenergetic diets with varying levels of glucose (20, 40 or 60% by weight) and fat (30, 22 or 14%, respectively, by weight) and were rested (R) or exercised (E) on a motorized treadmill at 20 m/min, 60 min/d (low intensity), 7 d/wk throughout pregnancy and lactation. Main effects and selected interactions of diet and exercise during pregnancy and diet, exercise and litter size during lactation were tested using 3 x 2 and 3 x 2 x 2 factorial designs, respectively. Neither diet nor exercise affected pregnancy outcomes. In contrast, during lactation, milk and mammary gland compositions and pup growth were altered. Exercise produced higher milk protein concentrations (40% glucose diet) and lower milk lactose concentrations (20% glucose diet). Exercise also lowered mammary gland fat content and produced higher milk fat concentrations. The 60% glucose diet resulted in the highest milk fat concentrations, but pups of dams fed the 40% diet were heavier on lactation d 15 than pups of dams fed the 60% diet. Taken together, these results support the claim of decreased availability of glucose to the mammary gland for lactose synthesis during chronic low intensity exercise. Additionally, the best lactation performance was not supported by a high carbohydrate (60% glucose), lower fat (14%) intake. A more moderate carbohydrate (40% glucose), higher fat (22%) intake promoted greater pup weights at weaning, suggesting an overlooked role for macronutrient composition in optimizing lactation performance.     

Effects of repeated gestation and lactation on milk n-6 fatty acid composition in rats fed on a diet rich in 18:2n-6 or 18:3n-6.

The present study examined the effect of repeated gestation and lactation on the levels of long-chain n-6 polyunsaturated fatty acids in rat milk fat, and examined whether such levels might be modulated by supplementing the diet of the lactating dams with either (g/kg) 50 safflower oil (SFO; containing 800 g 18:2n-6/kg), or 50 evening primrose oil (EPO; containing 720 g 18:2n-6 and 90 g 18:3n-6/kg). The milk was collected at three different times (days 1, 8 and 15) in each given lactation period from female Sprague-Dawley rats which were successively bred for four pregnancies and lactations. Results showed that dietary fat and breeding frequency had no significant effects on milk triacylglycerol content, but they modified the pattern of milk fatty acids in both triacylglycerol and phospholipid fractions. After three or four successive breedings rats fed on EPO produced milk containing less saturated but more monounsaturated and polyunsaturated fatty acids compared with those fed on SFO. During the course of lactation the levels of n-6 metabolites, e.g. 18:3n-6, 20:3n-6 and 20:4n-6, in milk fat declined progressively. However, they were consistently higher in the EPO group than in the SFO group. These findings suggest that the levels of long-chain n-6 metabolites in the milk fat may be increased through supplementing the maternal diet with 18:3n-6.     

共轭亚油酸对小鼠乳腺脂肪合成相关基因表达的作用研究

目的研究共轭亚油酸(CLA)对小鼠乳腺脂肪合成相关基因表达的影响。方法选取32只泌乳昆明鼠,随机分为对照组(2%花生油);0.5%CLA组(0.5%CLA+1.5%花生油);1.0%CLA组(1%CLA+1%花生油);1.5%CLA组(1.5%CLA+0.5%花生油),每组8只小鼠,从泌乳第4日饲喂至第14日,每日检测母鼠采食量、体重和仔鼠窝重,分析乳成分,采用荧光定量PCR检测对照组和1.5%CLA组母鼠乳腺组织脂肪合成相关基因的表达。结果在饲喂期间各组母鼠体重没有差异,饲料添加1.5%CLA显著减少了母鼠的采食量、仔鼠窝重和乳脂肪含量(P<0.05)。与对照组相比,1.5%CLA组母鼠乳腺组织的脂蛋白脂酶(LPL)、乙酰辅酶A羧化酶(ACACA)、硬脂酰辅酶A去饱和酶(SCD)和脂肪酸合成酶(FASN)的基因表达显著降低(P<0.05),并且转录因子固醇调节元件结合蛋白(SREBF)和过氧化物酶体增殖激活受体(PPARγ)的基因表达也显著下调(P<0.01)。结论饲料中加入1.5%CLA能够减少泌乳母鼠乳脂肪含量,抑制乳腺脂肪合成相关基因的表达。     

Low vitamin a intake affects milk iron level and iron transporters in rat mammary gland and liver

Marginal vitamin A deficiency is common and can result in a secondary iron (Fe) deficiency. A positive correlation between maternal Fe status and milk Fe was observed in lactating women supplemented with both vitamin A and Fe but not with Fe alone, suggesting effects of vitamin A on mammary gland Fe transport. We hypothesized that low vitamin A intake during lactation elicits differential effects on mammary gland and liver Fe transport and storage proteins, thus affecting milk Fe concentration but not maternal Fe status. We fed rats a control (CON, 4 RE/g) or a marginal vitamin A diet (AD, 0.4 RE/g) through midlactation. Effects on plasma, milk, liver and mammary gland Fe and vitamin A concentrations, and divalent metal transporter-1 (DMT1), ferroportin (FPN), ferritin (Ft), and transferrin receptor (TfR) expression were determined. Dams fed AD were not vitamin A or Fe deficient. Milk and liver vitamin A and Fe and mammary gland Fe concentrations were lower in rats fed AD compared with rats fed CON. Liver TfR expression was higher, whereas mammary gland TfR expression was lower in rats fed AD compared with rats fed CON. Liver Ft was unaffected, whereas mammary gland Ft was lower in rats fed AD compared with rats fed CON. Liver and mammary gland DMT1 and FPN protein levels were lower in rats fed AD compared with rats fed CON. Our results indicate that the mammary gland and liver respond differently to marginal vitamin A intake during lactation and that milk Fe is significantly decreased due to effects on mammary gland Fe transporters, putting the nursing offspring at risk for Fe deficiency.     

Maternal zinc deficiency raises plasma prolactin levels in lactating rats

There is an inverse relation between zinc (Zn) intake and plasma prolactin in men and nonpregnant women. Whether a relation exists in lactating women is unknown, despite the potential consequences of perturbations in prolactin regulation on lactation performance. We examined the effects of low Zn intake on prolactin concentration, the prolactin regulatory pathway in the pituitary gland, and lactation performance in lactating rats. Female rats were fed diets containing 7 (zinc deficient; ZD), 10 (marginally zinc deficient; MZD) or 25 mg Zn/kg (control) from 70 d preconception to lactation d 11. Rats were killed, pituitary glands dissected, and tissues and plasma collected and analyzed for prolactin concentration. Pituitary gland pituitary factor 1 (Pit-1), dopamine 2 receptor (D2R), and prolactin receptor mRNA expression were measured in the pituitary gland. Liver, mammary gland, plasma, and milk Zn were measured. Milk intake of the pups was also recorded. Plasma prolactin concentration was higher in rats fed the ZD (125.9 microg/L) diet compared with control rats (21.7 microg/L). Pituitary gland prolactin concentration was higher in rats fed the ZD diet (69.8 mg/g total protein) compared with controls (29.0 mg/g). Plasma Zn concentration was lower in rats fed the MZD and ZD diets, and mammary gland and milk Zn concentrations were lower in rats fed the ZD diet compared with control rats. Rats fed the ZD diet had lower D2R, prolactin receptor, and Pit-1 mRNA levels, whereas rats fed the MZD diet had lower prolactin receptor and Pit-1 mRNA levels compared with control rats. Milk intake was lower in pups of rats fed the MZD and ZD diets. Our results suggest that marginal Zn nutriture may compromise milk production despite increased prolactin levels. In addition, increased circulating prolactin concentration is not due to altered nursing behavior, but may be due to alterations in the prolactin regulatory pathway in the pituitary gland.     

Effects of lactation and nursing on tissue concentrations of polybrominated biphenyls and on microsomal enzyme activity in mammary gland and liver in maternal rats

Redistribution of polybrominated biphenyls (PBBs) during the recovery period following lactation resulted in concentrations of PBBs that were higher in mammary gland and lower in liver and fat than at the end of lactation. Hepatic arylhydrocarbon hydroxylase (AHH) and epoxide hydrolase (EH) activities were higher in PBB-treated rats during lactation than in the recovery period. However, transition from lactating to dry state had no effect on activity of mammary gland AHH in rats treated with PBBs. Microsomal enzyme activity and concentrations of PBBs in mammary gland and liver were reduced by nursing a second litter. Although redistribution and excretion of PBBs resulted in alterations in microsomal enzyme activity, all rats exposed to 100 ppm PBBs had microsomal enzyme activity in liver and mammary gland that was higher than that in controls. Persistent stimulation of mammary gland and hepatic microsomal enyzmes while mothers are exposed to PBBs may affect not only mothers and offspring suckling but subsequent progeny as well.     

Lipases in human milk: effect of gestational age and length of lactation on enzyme activity.

Human milk contains two lipases, bile salt-stimulated lipase (BSSL) and lipoprotein lipase (LPL). In the mammary gland, LPL provides long-chain fatty acid for milk fat synthesis. LPL has no known function in milk, but has been implicated in milk fat hydrolysis during cold storage. BSSL may have an important role in infant fat digestion. The aims of the present studies were to assess (1) the methodological validity of using whole milk to analyze BSSL activity, (2) the longitudinal variation of BSSL and LPL activity in the milk of mothers delivering premature and full-term infants, and (3) the stability of BSSL and LPL activity during cold storage. Diluted whole milk and purified BSSL were shown to have similar characteristics. LPL activity was equally stable at -20 and -70 degrees C, whereas BSSL activity was higher in milks stored at -70 than at -20 degrees C (38.8 +/? 0.88 vs 33.3 +/? 0.87 U/ml milk, respectively; 1U = 1 mumol free fatty acid release/min). Levels of BSSL activity in preterm and term milk were similar. LPL activity tended to be higher in term milk. Overall, BSSL activity showed significant longitudinal variation, being highest at 1 and 3 weeks of lactation (43.2 +/? 0.04 and 42.6 +/? 1.03 U/ml milk, respectively). For LPL, the longitudinal pattern of activity depended upon the length of pregnancy. Implications for infant nutrition and mammary gland biology are discussed.     

Some metabolic effects on lactating rats of a low-energy diet restricted in good-quality protein

Adult female Sprague-Dawley rats were fed ad libitum during pregnancy and lactation a control diet (CD; 16.1 kJ/g) or a low-energy diet with wheat gluten as the main protein source (LED; 13.3 kJ/g). Body weight, food intake, resting energy expenditure, respiratory quotient and substrate use by the mammary gland were measured. After the animals had been killed, the parametrial and retroperitoneal fat pads were weighed. The mean food intake (g) of the two groups of rats was similar, resulting in a lower energy intake by the LED rats, significantly different during the last 2 weeks of lactation. The mean body weight of both dams and pups in the LED group was lower, starting at day 9 of lactation. The resting energy expenditure increased gradually during lactation in the control group, whereas this increase was not seen in rats of the LED group in the last week of lactation. Rats that had fasted overnight had a respiratory quotient of 0.7 or less, whereas for rats that had been fed, the mean respiratory quotient was over 1.0. Under both conditions, rats showed ketonuria. The arteriovenous difference in 3-hydroxybutyrate level was higher and those for glucose, lactate and triacylglycerol were lower across the mammary glands of LED rats. The parametrial fat depot weighed less in LED rats. Reducing the increase in resting energy expenditure and using ketone bodies to a greater extent as fuels may represent important mechanisms in the LED dams to cover the energy cost of milk production.     

Dietary conjugated linoleic acids alter adipose tissue and milk lipids of pregnant and lactating sows

Conjugated linoleic acids (CLA) have been shown to affect fatty acid synthesis in various tissues. The objective of the study was to compare the effect of a commercial source of CLA with a linoleic acid-enriched oil (LA), supplied to 12 multiparous sows during gestation and lactation, on adipose tissue and milk fatty acid composition. The CLA isomers detected in the CLA oil were (in order of magnitude) c9,t11; t10,c12; c9,c11; t9,t11/t10,t12 and c10,c12 and amounted to 58.9 g/100 g fat. Biopsies were taken from the backfat on d 7 and 97 of gestation and milk samples were collected on d 2, 9, 16 and 23 after farrowing. Collection of colostrum and mature milk samples took place at 1100 h for sows who farrowed in the morning or at 1500 h for those who farrowed in the afternoon. All major CLA isomers in the supplement were transferred to the tissue and milk fat and, compared with the LA group, significantly increased saturated fatty acid and decreased monounsaturated fatty acid levels in the tissue and milk. These findings suggest a distinct involvement of CLA in the de novo fatty acid synthesis and desaturation process in the adipose tissue and mammary gland. Estimated transfer efficiency of dietary CLA isomers was 41-52% for the backfat and 55-69% for the mature milk. The incorporation and uptake efficiency seemed to be selective with the highest values found for c9,t11-CLA. Overall, dietary CLA supplementation of sows during gestation and lactation markedly altered backfat and milk fatty acid composition.     

Milk lipid synthesis and secretion during milk stasis in the rat

The lipid content of milk expressed from rats decreased from 15.8% wt/vol within 1 h of the removal of the pups to 4.2% in samples obtained 12 h after the removal of the pups. The protein and lactose concentrations were unchanged. Analysis of gland homogenates showed that lactose and total lipid accumulated throughout the 12 h period of milk stasis. The rate of mammary fatty acid synthesis in vivo determined using tritiated water was not significantly altered by 12 h of milk stasis, and analysis of the milk and gland fatty acids showed that the relative proportions of de novo synthesized fatty acids (medium-chain fatty acids) and those derived from the circulation (16 and 18 C acids) had been maintained. Light and electron microscopy showed the accumulation of considerable quantities of lipid within the lumen of the alveoli even while the pups were still suckling. Twelve hours after the removal of the pups there was not only a marked increase in the lumenal lipid, but also considerable lipid trapped in the epithelial cells. In rats where the nipples were ligated unilaterally and allowed to be suckled for 12 h, the milk from the ligated glands contained significantly less lipid than that from the suckled glands but more lipid than from milk of rats removed from their pups for 12 h. Administration of oxytocin during 12 h of milk stasis significantly increased the milk lipid content.     

Lipases in human milk: effect of gestational age and length of lactation on enzyme activity

Human milk contains two lipases, bile salt-stimulated lipase (BSSL) and lipoprotein lipase (LPL). In the mammary gland, LPL provides long-chain fatty acid for milk fat synthesis. LPL has no known function in milk, but has been implicated in milk fat hydrolysis during cold storage. BSSL may have an important role in infant fat digestion. The aims of the present studies were to assess (1) the methodological validity of using whole milk to analyze BSSL activity, (2) the longitudinal variation of BSSL and LPL activity in the milk of mothers delivering premature and full-term infants, and (3) the stability of BSSL and LPL activity during cold storage. Diluted whole milk and purified BSSL were shown to have similar characteristics. LPL activity was equally stable at -20 and -70 degrees C, whereas BSSL activity was higher in milks stored at -70 than at -20 degrees C (38.8 +/- 0.88 vs 33.3 +/- 0.87 U/ml milk, respectively; 1U = 1 mumol free fatty acid release/min). Levels of BSSL activity in preterm and term milk were similar. LPL activity tended to be higher in term milk. Overall, BSSL activity showed significant longitudinal variation, being highest at 1 and 3 weeks of lactation (43.2 +/- 0.04 and 42.6 +/- 1.03 U/ml milk, respectively). For LPL, the longitudinal pattern of activity depended upon the length of pregnancy. Implications for infant nutrition and mammary gland biology are discussed.     

Regulation of fat synthesis by conjugated linoleic acid: lactation and the ruminant model

Conjugated linoleic acid (CLA) isomers effect an impressive range of biological processes including the ability to inhibit milk fatty acid synthesis. Although this has been demonstrated in several mammals, research has been most extensive with dairy cows. The first isomer shown to affect milk fat synthesis during lactation was trans-10, cis-12 CLA, and its effects have been well characterized including dose-response relationships. Recent studies have tentatively identified 2 additional CLA isomers that regulate milk fat synthesis. Regulation by CLA occurs naturally in dairy cows when specific CLA isomers produced as intermediates in rumen biohydrogenation act to inhibit milk fat synthesis; this physiological example of nutritional genomics is referred to as diet-induced milk fat depression. Molecular mechanisms for the reduction in mammary lipid synthesis involve a coordinated down-regulation of mRNA expression for key lipogenic enzymes associated with the complementary pathways of milk fat synthesis. Results provide strong evidence of a role for sterol response element-binding protein 1 and Spot 14 in this translational regulation. Effects of CLA on body fat accretion have also been investigated in nonlactating animals, but CLA effects on mammary fatty acid synthesis occur at an order-of-magnitude lower dose and appear to involve very different mechanisms than those proposed for the antiobesity effects of CLA. Overall, results demonstrate the unique value of cows as a model to investigate the role of CLA in the regulation of milk fat synthesis during lactation.     

Marginal maternal Zn intake in rats alters mammary gland Cu transporter levels and milk Cu concentration and affects neonatal Cu metabolism

Marginal zinc intake is common and leaves women particularly vulnerable to Zn deficiency due to increased demand for Zn as a consequence of reproduction. Zn deficiency during pregnancy and lactation has been associated with secondary affects on copper metabolism in the offspring; however, the underlying mechanisms are unknown. The effects of marginal maternal Zn intake on maternal and neonatal Cu metabolism were determined in rats. Plasma, milk and tissue Cu and Zn concentrations and plasma and milk ceruloplasmin (Cp) activity were measured in dams fed a control (CON, 25 mg Zn/kg diet) or a marginal Zn diet (ZD, 10 mg Zn/kg diet) and their suckling pups. There was no effect on maternal tissue Cu or Zn or milk Zn concentration; however, plasma Cp activity was higher in dams fed ZD, suggesting that Cp activity may be a useful marker for identifying marginal Zn status. Rats fed ZD had high mammary gland Ctr1, Atp7A and Atp7B levels, milk Cp activity and Cu concentration. Immunostaining and differential centrifugation indicated that ZD also altered Ctr1 and Atp7A localization in the mammary gland. Pups from dams fed ZD had higher small intestine Cu and lower plasma Cu than CON pups. These results suggest that marginal maternal Zn intake during pregnancy and lactation increase mammary gland Cu transporter levels and alter their localization, resulting in high milk Cu levels, possibly in response to transiently elevated plasma Cu levels. The combination of high milk Cu concentration and immature neonatal Cu transport exposes the suckling neonate to excess Cu; however, whether this occurs in humans is not yet known.     

Iron transporters in rat mammary gland: effects of different stages of lactation and maternal iron status

BACKGROUND: Mechanisms regulating iron transfer from maternal circulation into milk are yet unknown. Whether intestinal iron transporters, divalent metal transporter 1 (DMT1) and ferroportin 1 (FPN1), are present in the mammary gland and are involved in iron transfer into milk are unknown. OBJECTIVE: The objective was to examine DMT1 and FPN1 in rat mammary gland at different stages of lactation and to evaluate the effects of maternal iron status. DESIGN: Rats were fed either 35 mg Fe (control rats) or 8 mg Fe (low-iron rats) per kg diet for 3 wk and were fed the same diet throughout pregnancy and lactation. Mammary gland DMT1, FPN1, transferrin receptor, and ferritin were examined in control rats on days 1, 5, 10, and 20 of lactation and in low-iron rats on days 10 and 20 of lactation. Tissue and milk iron were measured. RESULTS: Milk iron, DMT1, and FPN1 decreased throughout lactation. Iron status was compromised in low-iron rats, whereas milk iron was maintained. On day 10 of lactation, mammary gland iron and ferritin were lower in the low-iron rats. DMT1, FPN1, and transferrin receptor values were unchanged; however, a smaller-size DMT1 protein was observed in the low-iron rats. On day 20, transferrin receptor increased in the low-iron rats, whereas mammary gland iron, ferritin, DMT1, and FPN1 were unchanged. CONCLUSIONS: The results show that DMT1 and FPN1 concentrations are higher during early lactation and are possibly involved in iron transfer into milk. Mammary gland regulation of DMT and FPN1 during low iron status appears to be different from that in the intestine.     

Conjugated linoleic acid is a growth factor for rats as shown by enhanced weight gain and improved feed efficiency

We studied the effect of conjugated linoleic acid (CLA) on rat development and growth. Primigravid female Fischer rats were fed control or CLA-supplemented (0.25% or 0.5% CLA) diets during gestation and/or lactation. Conjugated linoleic acid was incorporated into milk fat and tissue lipids proportional to the level of CLA fed and the duration of CLA feeding. Conjugated linoleic acid was incorporated into fetal and neonatal tissues; it did not affect litter size nor induce apparent abnormalities. To the contrary, feeding CLA to the dams during gestation and lactation improved the postnatal body weight gain of pups (P < 0.05), measured on d 10 of lactation. Pups that continued to receive the CLA-supplemented diet after weaning had significantly greater body weight gain and improved feed efficiency relative to control animals (P < 0.05).     

Reduction of the intake of food and water is responsible for reduction of litter growth when dams are treated with a progesterone antagonist

Treatment of lactating rats with the anti-progestin Mifepristone or Onapristone adversely affects growth of their litters. The present studies aimed to elucidate the underlying mechanism. The treatment did not interfere with the behavioural interactions between mothers and pups, which are required for normal litter growth. Treatment with the antagonists had a stimulatory action on ovarian oestrogen production. However, ovarian hormones did not play a role in litter growth impairment, as this also occurred with lactating ovariectomized rats. Treatment with anti-progestins did not affect the concentrations of the macronutrients in milk (protein, lactose and lipid), nor did it change the fatty acid composition of lipid. Reduced litter growth was not related to a possible direct effect of exposure of the suckling young to the drugs via the milk. Direct injections into them unequivocally affected adrenal gland and testicular development, but did not affect their body-weight development. Milk secretion, as measured by the milk weight accumulating during 6 or 24 h following sudden removal of litters in advanced lactation, was not impaired by the treatments. However, the ingestion of food and water by dams treated with Mifepristone was significantly below that of control animals. It is concluded that litter growth impairment during treatment of lactating rats with anti-progestin results from the reduction of the intake of food and water by the mother.