Dietary conjugated linoleic acids lower the triacylglycerol concentration in the milk of lactating rats and impair the growth and increase the mortality of their suckling pups

Recent studies showed that conjugated linoleic acids (CLA) lower triacylglycerol concentrations in the milk of lactating animals. This study was performed to determine the reasons for this phenomenon; we also investigated whether there is a relation between altered lipid metabolism in the liver and the reduction in milk triacylglycerols in rats fed CLA. Two groups of female rats were fed diets containing 0 [sunflower oil (SFO) group] or 14.7 g/kg diet of a CLA mixture (CLA group) at the expense of sunflower oil during growth, pregnancy, and lactation. CLA-fed rats had 49 and 80% lower mRNA concentration and activity of fatty acid synthase, respectively, a 51% lower mRNA concentration of lipoprotein lipase (LPL) in their mammary glands at d 17 of lactation, and a 46% lower milk fat content than SFO rats (P < 0.05). Although CLA rats had lower concentrations of triacylglycerols in the liver than SFO rats (20.8 +/- 2.6 vs. 62.6 +/- 27.7 micromol/g, P < 0.05), concentrations of triglycerides in plasma, which are the substrates of LPL, did not differ between the groups. Moreover, the number of pups per litter, litter weights, and pup weights at d 17 of lactation were 41, 35, and 22% lower, respectively, in the CLA group than in the SFO group. In conclusion, the present study suggests that dietary CLA reduces triacylglycerol concentrations in the milk via reduced de novo fatty acid synthesis in the mammary gland and an impaired uptake of fatty acids from lipoproteins into the mammary gland. This might be the reason for reduced growth rates and an increased mortality of suckling pups.     

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.     

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.     

Fatty acids and retinyl esters of rat milk: effects of diet and duration of lactation

This study was initiated to explore the quantitative and qualitative differences in milk total fatty acids and milk retinyl esters when either hydrogenated or nonhydrogenated fat is fed during pregnancy and lactation. Rats were fed diets containing 10% by weight of corn oil or partially hydrogenated corn oil. Milk was collected on d 1, 8 and 14 of lactation and analyzed for protein, total fatty acids, fatty acid pattern, and retinyl ester pattern. Whereas diet produced no quantitative differences in milk protein or total fatty acids, the pattern of milk fatty acids varied significantly. Rats fed corn oil produced milk having more medium-chain saturated fatty acids, less long-chain monoenoic fatty acids, and more polyunsaturated fatty acids compared to those fed hydrogenated corn oil. Rats fed hydrogenated corn oil produced milk fat having 21-26% of the trans fatty acid, elaidic acid. Significant differences were also observed with duration of lactation: medium-chain fatty acids increased three to fourfold between d 1 and 8, where cis-monoenes and polyunsaturated fatty acids declined. The pattern of milk retinyl esters strongly reflected, but was not identical to, that of total milk fat. Comparing d 14 milk from rats fed corn oil with that from rats fed hydrogenated corn oil, medium-chain esters of retinol constituted 24 and 11% of total retinyl esters, whereas saturated long-chain fatty acid esters constituted 52 and 44%, respectively. trans Fatty acid esters of retinol comprised 24% of vitamin A esters in milk of rats fed hydrogenated fat. These data provide evidence that the composition of milk retinyl esters, as well as that of total milk fat, is determined both by the type of fatty acids from diet and from diet-related differences in de novo synthesis of fatty acids within the mammary gland and other tissues.     

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.     

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.     

Lipid composition in human breast milk from Granada (Spain): changes during lactation

OBJECTIVE: To determine possible differences of composition in the course of lactation, phospholipid (PL) classes (phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, phosphatidylcholine, and sphingomyelin) and fatty acid composition of PL and triacylglycerol (TGs) fractions of milk fat were analyzed in 66 samples from mothers from Granada (Spain) who gave birth to full-term infants. Analyses included colostrum, transitional milk, and mature milk. METHODS: After milk fat extraction, PLs and TGs were separated by thin-layer chromatography and fatty acids of each fraction were converted into their methyl esters, which were analyzed by gas chromatography. PL classes were determined by high-performance liquid chromatography using an evaporative light-scattering detector. RESULTS: Mature human milk showed a lower content (P = 0.020) of PLs than did the other milks. Percentage of sphingomyelin was constant for all stages of lactation, whereas the percentage of phosphatidylcholine in mature milk was significantly lower (P < 0.05) than in colostrum and transitional milk. TGs in mature human milk contained lower percentages (P < 0.001) of arachidonic acid, docosahexaenoic acid, and nervonic acid. Docosahexaenoic acid and nervonic acid also showed a significant decrease (P < 0.001) in total PLs from colostrum and mature milk. CONCLUSIONS: The composition of PL classes and fatty acids in PLs and TGs in milk of mothers in Granada (Southern Europe) is different from that in milk from mothers in other parts of the world. In addition, the ratio of long-chain polyunsaturated fatty acids delivered in the form of PLs to long-chain polyunsaturated fatty acids delivered in the form of triacylglycerols diminishes as lactation proceeds.     

Effect of dietary levels of corn oil on maternal arachidonic acid synthesis and fatty acid composition in lactating rats

OBJECTIVE: We examined the effect of different amounts of dietary corn oil rich in linoleic acid (LA) on the endogenous synthesis of arachidonic acid (AA), uptake of its precursor LA, and fatty acid composition of tissues involved in the supply of long-chain polyunsaturated fatty acids for milk synthesis. METHODS: Female Sprague Dawley rats received one of the following diets during pregnancy and lactation: a low-lipid diet (LLD; 2%), an adequate-lipid diet (ALD; 5%), or a high-lipid diet (HLD; 10%). Lipids were provided by corn oil. On day 12 of lactation we measured the endogenous synthesis of AA and quantified the conversion of (13)C-LA to (13)C-AA and the metabolic fate of (13)C-LA from all dietary groups. RESULTS: The LLD rats demonstrated larger amounts of endogenous synthesis of (13)C-AA and more dietary (13)C-LA transferred to the mammary gland (MG) than HLD rats during lactation. The proportion of medium-chain fatty acids was higher in the MG, milk clot, and liver of LLD than of HLD rats. Daily volume and 24-h yield of lipids and energy were lower in LLD rats than in HLD rats. Measurements of milk composition demonstrated that fat concentration significantly increased as lipid concentration increased in the diet. CONCLUSION: These results suggest that maternal adaptations used to compensate for diets deficient in long-chain polyunsaturated fatty acids include increased endogenous synthesis of AA and elevated uptake of LA in the MG and increased synthesis of medium-chain polyunsaturated fatty acids. It appears that the MG and liver participate together for AA synthesis for milk when this fatty acid is not provided in the diet.     

Zinc transporters in the rat mammary gland respond to marginal zinc and vitamin A intakes during lactation

Marginal intake of zinc and vitamin A is common during lactation and a deficiency of one micronutrient can result in a secondary deficiency of the other. However, the resistance of milk zinc (Zn) concentration to changes in dietary Zn or vitamin A indicates tight regulation of mammary gland Zn transport. Although several mammalian proteins have been identified and implicated in Zn transport, the mechanisms responsible for mammary gland Zn transport and their regulation by dietary Zn and vitamin A are unknown. In this study, we identified mammary gland Zn transporters and determined effects of marginal Zn and vitamin A intakes on their levels. Rats were fed a control [25 mg Zn/kg, 4 retinol equivalents (RE)/g], a low Zn (10 mg Zn/kg), a low vitamin A (0.4 RE/g), or a low Zn (10 mg Zn/kg) and vitamin A (0.4 RE/g) diet throughout lactation. ZnT-1, ZnT-2 and ZnT-4 were identified in the mammary gland and localized to the serosal membrane (ZnT-1) or intracellularly (ZnT-2 and ZnT-4) by immunostaining. Rats fed a low Zn or low vitamin A diet had lower ZnT-1 protein and higher ZnT-4 mRNA expression and protein levels compared with controls. There was a significant interaction between dietary Zn and vitamin A on zinc transporter mRNA expression and protein levels. Although total mammary gland Zn was not affected, mammary gland metallothionein levels were lower in rats fed low Zn and higher in rats fed low vitamin A, suggesting different mechanisms regulating zinc transporter levels. These results indicate that milk Zn level is maintained through coordinated regulation of mammary gland zinc transporters and documents an effect of vitamin A on zinc homeostasis at the molecular level during lactation.     

Milk and plasma lipid composition in a lactating patient with type I hyperlipoproteinemia

This report describes studies on the plasma and milk lipid composition of a patient with primary Type I hyperlipoproteinemia who had been followed through her second pregnancy. Post-partum she lactated, supplying milk for assay. It was abnormal in the low content of its total lipid and in the bizarre composition of its fatty acids. The proportion of long chain fatty acids was unusually low, and that of medium chain fatty acids unusually high. Furthermore, the fatty acids of the patient's milk differed greatly from those of her plasma triglycerides. This was in marked contrast to normal nursing mothers' milk, in which the fatty acid composition is comparable to that of plasma triglycerides. The patient's milk fatty acids were shorter in chain length and deficient in essential fatty acids. During the time of lactation, the patient remained hyperlipidemic and her post-heparin plasma had no lipolytic activity. These data and the differences between the plasma and milk fatty acids suggested that in the patient the circulating triglyceride fatty acids did not enter the mammary gland. Without preformed fatty acids entering it from plasma or adipose tissue, the lactating breast apparently synthesized fatty acids de novo. These newly synthesized fatty acids were of medium, rather than long chain length. This accounted for the abundance of medium chain length triglycerides in the patient's milk. The studies suggested that the deficit of lipoprotein lipase in Type I hyperlipoproteinemia extended to the mammary gland.     

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.     

Lipoprotein lipase activity in skeletal muscle and brown adipose tissue of pregnant and lactating rats

Changes in lipoprotein lipase (LPL) activity during pregnancy and lactation were followed in skeletal muscles and interscapular brown adipose tissue (BAT) of rats fed two diets differing in energy density (high carbohydrate or high fat). Rats were decapitated after 7, 19 or 21 d of pregnancy or after 3 or 12 d of lactation. Virgin rats and females separated from their litter just after delivery were used as nonpregnant and nonlactating controls, respectively. Blood was collected for determination of plasma glucose, triglycerides (TG) and nonesterified fatty acids (NEFA). Soleus, extensor digitorum longus (EDL), diaphragm and interscapular BAT were rapidly removed and frozen in liquid nitrogen for LPL activity measurement. LPL activity was not significantly higher in muscles and BAT of virgin rats fed the high fat diet than in those of rats fed the high carbohydrate diet. No significant change of skeletal muscle LPL activity was observed during pregnancy, regardless of the diet fed. Although BAT exhibited a transitory hypertrophy during pregnancy, its LPL activity was not significantly altered; during lactation BAT lost weight and its LPL activity dropped sharply when either diet was fed, leaving more TG available for milk production.     

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.     

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.     

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.     

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.     

Effect of dietary seal and fish oils on triacylglycerol metabolism in rats

Eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids were distributed mainly in the sn-1 and 3 positions of seal oil triacylglycerol and in the sn-2 position of fish oil triacylglycerol. Seal oil or fish oil-rich fats having constant polyunsaturated/monounsaturated/saturated fatty acids and n-6/n-3 polyunsaturated fatty acid (PUFA) ratios were fed to rats for 3 wk. Control rats were fed on a fat containing linoleic acid as the sole PUFA. Seal oil more effectively lowered serum and liver triacylglycerol concentrations than fish oil. The activities of fatty acid synthase (FAS), glucose-6-phosphate dehydrogenase (G6PDH) and hepatic triacylglycerol lipase (HTGL) were significantly lower in the seal oil group than in the control group, whereas the activity of HTGL was significantly lower and the hepatic peroxisomal beta-oxidation and activity of lipoprotein lipase (LPL) in adipose tissue were significantly higher in the fish oil group than in the control group. These observations suggest that the predominant hypotriacylglycerolemic effect of seal oil is caused by the suppression of fatty acid synthesis.     

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.     

Acute administration of cefepime lowers L-carnitine concentrations in early lactation stage rat milk

Our study investigated the potential for important in vivo drug-nutrient transport interactions at the lactating mammary gland using the L-carnitine transporter substrates, cefepime and L-carnitine, as proof-of-concept. On d 4 (n = 6/treatment) and d 10 (n = 6/treatment) of lactation, rats were administered cefepime (250 mg/h) or saline by continuous i.v. infusion (4 h). Serum and milk L-carnitine and cefepime concentrations were quantified by HPLC-UV. In whole mammary gland, organic cation/carnitine transporter (OCTN)1, OCTN2, OCTN3, amino acid transporter B(0,+) (ATB(0,+)), and L-carnitine transporter 2 expression were determined by quantitative RT-PCR and by western blot and immunohistochemistry when possible. Cefepime caused a 56% decrease in milk L-carnitine concentrations on lactation d 4 (P = 0.0048) but did not affect milk L-carnitine at lactation d 10 or serum L-carnitine concentrations at either time. The mean L-carnitine and cefepime milk:serum ratios (M/S) decreased from 9.1 +/- 0.4 to 4.9 +/- 0.6 (P < 0.0001) and 0.89 +/- 0.3 to 0.12 +/- 0.02 (P = 0.0473), respectively, between d 4 and d 10 of lactation. In both groups, OCTN2 (P < 0.0001), OCTN3 (P = 0.0039), and ATB(0,+) (P = 0.004) mRNA expression and OCTN2 protein (P < 0.0001) were higher in mammary glands at d 4 of lactation compared with d 10. Immunohistochemistry revealed OCTN1 and OCTN2 localization in the mammary alveolar epithelium and OCTN3 expression in the interstitial space and blood vessel endothelium. In conclusion, cefepime significantly decreased milk L-carnitine concentrations only at d 4 of lactation. Relative to d 10, enhanced expression of OCTN2 and ATB(0,+) in mammary glands at d 4 of lactation and higher M/S (L-carnitine and cefepime) suggests cefepime competes with L-carnitine for L-carnitine transporters expressed in the lactating mammary gland to adversely affect L-carnitine milk concentrations and these effects depend upon lactation stage.