Lipoprotein Lipase Activity In Mammary Gland Research Articles

Passive immunization of lactating mice with stanniocalcin-1 antiserum reduces mammary gland development, milk fat content, and postnatal pup growth

During pregnancy and lactation in rodents, stanniocalcin-1 (STC-1) production by the ovaries is upregulated markedly and released into the circulation. The mammary glands are one target of this systemically delivered hormone. The purpose of this study was to lower serum levels of STC-1 in lactating mice through passive immunization so as to monitor the effects on mammary gland function and postnatal pup growth. Passive immunization significantly reduced circulating hormone levels, and pup growth was significantly compromised (30%), even though control and experimental litters had ingested equal amounts of milk. When mammary glands were analyzed, the alveolar area was significantly reduced in antibody-treated mothers. An analysis of milk composition revealed no changes in lactose, protein, or electrolyte levels but an approximately 40% reduction in triglyceride levels. The latter was due to a significant reduction in mammary gland lipoprotein lipase activity and led to a significant buildup of triglycerides in the serum. Body fat content was also significantly reduced in pups from antibody-treated mothers, whereas pup fecal fat content was increased. In mothers, passive immunization also caused significant behavioral effects, in particular, increased locomotor and hindleg rearing activities. Collectively, the results suggest that systemically derived STC-1 has important effects on mammary gland development and the transfer of serum-based triglycerides into milk. Locomotor effects suggest that STC-1 also has a role in maternal behavior.

Streptozotocin-induced diabetes decreases mammary gland lipoprotein lipase activity and messenger ribonucleic acid in pregnant and nonpregnant rats.

Diabetes mellitus is associated with a reduction of lipoprotein lipase (LPL) activity in adipose tissue and development of hypertriglyceridemia. To determine how a condition of severe insulin deficiency affects mammary gland LPL activity and mRNA expression during late pregnancy, streptozotocin (STZ) treated (40 mg/kg) and non-treated (control) virgin and 20 day pregnant rats were studied. In control rats, both LPL activity and mRNA were higher in pregnant than in virgin rats. When compared to control rats, STZ-treated rats, either pregnant or virgin, showed decreased LPL activity and mRNA content. Furthermore, mammary gland LPL activity was linearly correlated with mRNA content, and either variable was linearly correlated with plasma insulin levels. Thus, insulin deficiency impairs the expression of LPL in mammary glands, revealing the role of insulin as a modulator of the enzyme at the mRNA expression level.

Effects of tri-iodothyronine administration on the disposal of oral [1-14C]triolein, lipoprotein lipase activity and lipogenesis in the rat during lactation and on removal of the litter

The effect of tri-iodothyronine (T3) administration on the utilization of dietary [14C]lipid by the mammary gland and adipose tissue of lactating and litter-removed rats was studied. (1) After an oral load of [1-14C]triolein, the lactating rats treated with T3 (50 micrograms/100 g body wt.) over 24 h showed an increase in 14CO2 production and a decrease in the total [14C]lipid transferred through the mammary gland that was paralleled by a decrease in tissue lipoprotein lipase (LPL) activity. (2) T3 administration decreased plasma prolactin in the lactating rats. Prolactin replacement in T3-treated rats restored LPL activity in the mammary gland, but did not increase the amount of dietary [14C]lipid transferred to the milk. (3) Chronic T3 administration (4 days) to lactating rats did not affect pup growth or the lipogenic rate in the mammary gland. (4) The administration of T3 to litter-removed rats inhibited the increase of LPL activity in white adipose tissue and decreased the accumulation of dietary [14C]lipid. This decrease was accompanied by increased 14CO2 production and [14C]lipid accumulation in skeletal muscle and heart. (5) It is concluded that hyperthyroidism depresses LPL activity in mammary gland and white adipose tissue, but not in muscle. The increased accumulation of [14C]lipid in muscle and increased production of 14CO2 in lactating and in litter-removed rats treated with T3 is in part due to the decreased total LPL in mammary gland and adipose tissue respectively, which are therefore less able to compete with muscle for the available plasma triacylglycerols.

Tissue-specific effects of rapid tumour growth on lipid metabolism in the rat during lactation and on litter removal

1. The effect of tumour burden on lipid metabolism was examined in virgin, lactating and litter-removed rats. 2. No differences in food intake or plasma insulin concentrations were observed between control animals and those bearing the Walker-256 carcinoma (3-5% of body wt.) in any group studied. 3. In virgin tumour-bearing animals, there was a significant increase in liver mass, blood glucose and lactate, and plasma triacylglycerol; the rate of oxidation of oral [14C]lipid to 14CO2 was diminished, and parametrial white adipose tissue accumulated less [14C]lipid compared with pair-fed controls. 4. These findings were accompanied by increased accumulation of lipid in plasma and decreased white-adipose-tissue lipoprotein lipase activity. 5. In lactating animals, tumour burden had little effect on the accompanying hyperphagia or on pup weight gain; tissue lipogenesis was unaffected, as was tissue [14C]lipid accumulation, plasma [triacylglycerol] and white-adipose-tissue and mammary-gland lipoprotein lipase activity. 6. On removal (24 h) of the litter, the presence of the tumour resulted in decreased rates of lipogenesis in the carcass, liver and white and brown adipose tissue, decreased [14C]lipid accumulation in white adipose tissue, but increased accumulation in plasma and liver, increased plasma [triacylglycerol] and decreased lipoprotein lipase activity in white adipose tissue. 7. The rate of triacylglycerol/fatty acid substrate cycling was significantly decreased in white adipose tissue of virgin and litter-removed rats bearing the tumour, but not in lactating animals. 8. These results demonstrate no functional impairment of lactation, despite the presence of tumour, and the relative resistance of the lactating mammary gland to the disturbance of lipid metabolism that occurs in white adipose tissue of non-lactating rats with tumour burden.

Lipid metabolism in pregnancy.

On the basis of bibliographic references and new own data, major adaptations of lipid metabolism occurring at late gestation are reviewed. Maternal hypertriglyceridemia at late gestation results from the juxtaposition of several factors: enhanced adipose tissue lipolysis facilitating the availability to the liver of substrates for triglyceride synthesis and contributing to augmented flux of very low density lipoproteins (VLDL) into the circulation; maternal hyperphagia and unmodified gut lipid absorption increasing chylomicron formation from dietary lipid; reduced lipoprotein lipase (LPL) activity in extrahepatic tissues (especially adipose tissue) which does not allow a triglyceride removal proportional to their enhanced production. It is proposed that these changes are also responsible for the altered composition of VLDL in late pregnancy. In conditions of food deprivation the use of glycerol released from adipose tissue as preferential gluconeogenic substrate, and the enhanced maternal ketogenesis warrants the availability of fuels for the fetus. Just prior to parturition the increase in mammary gland LPL activity is responsible for the reduction in circulating triglycerides and prepares the mother for lactation.

The effects of Δ1-tetrahydrocannabinol on mammary gland growth, enzyme activity and plasma prolactin levels in the mouse

Δ 1-tetrahydrocannabinol ( Δ 1-THC), a highly lipid soluble and active principle of cannabis, was injected each day (25 mg/kg) s.c. in mice from the estimated 13th day of pregnancy. Δ 1-THC-treated mice showed no increase in the wet weight or DNA content of their mammary glands during the period of investigation from before parturition until the 12th day post-partum. A marked increase in mammary-gland lipoprotein lipase activity was found in control mice at parturition and this was suppressed by Δ 1-THC. Prolactin rose to a peak level in plasma earlier in lactation in the control mice than in the Δ 1-THC-treated mice. This delayed rise in plasma prolactin due to Δ 1-THC may account for the depression of mammary gland growth and development by the drug and for the delay in the appearance of high activities of lipoprotein lipase until later in lactation.

Lipoprotein lipase activity of adipose and mammary tissue and plasma triglyceride in pregnant and lactating rats

1. 1. The effect of pregnancy and lactation on lipoprotein lipase activity in adipose and mammary tissues and on plasma triglyceride concentration were studied in the rat. 2. 2. Plasma triglyceride concentration, 0.9 mM in control rats, increased 3-fold between the 12th and 20th days of pregnancy to a peak of 3.3 mM, and then decreased 50% during the next 2 days. It increased again at parturition, on the 22nd–23rd days of pregnancy, to 3.0 mM, and then fell sharply and remained below 1.0 mM throughout lactation. 3. 3. Lipoprotein lipase activity in parametrial adipose tissue, 12 units/g in control rats, increased 2-fold between the 9th and 12th days of pregnancy and then decreased slightly during the next 7 days, (1 unit of lipoprotein lipase activity = 1 μmole of triglyceride hydrolyzed per h.) It decreased on the 20th day to 5 units/g, reached 2 units/g at parturition, and remained below 2 units/g throughout lactation. 4. 4. Lipoprotein lipase activity in the inguinal-abdominal mammary glands increased very slowly during the first 20 days of pregnancy, from 0.9 units/g to 7 units/g. It then increased the next day to 21 units/g, decreased sharply at parturition to 6 units/g, and increased after parturition to more than 40 units/g. Lipoprotein lipase activity in mammary gland remained high as long as the mother suckled. 5. 5. Nonsuckling for 9 or more h decreased mammary gland lipoprotein lipase activity to near zero and increased plasma triglyceride concentration to 3 mM. Nonsuckling also increased lipoprotein lipase activity in adipose tissue. 6. 6. Ligation of the lactiferous ducts of the inguinal-abdominal glands on one side markedly reduced the lipoprotein lipase activity in these glands but not that in the contralateral, suckled glands. 7. 7. Plasma triglyceride concentration was inversely related to the lipoprotein lipase activity in mammary tissue during the last 2 days of pregnancy and throughout lactation. 8. 8. It is suggested that the changes in lipoprotein lipase activity of adipose and mammary tissues that occur during late pregnancy and lactation serve to divert dietary lipid from storage in adipose tissue to mammary glands for milk formation.