Metabolism of sheep adipose tissue during pregnancy and lactation. Adaptation and regulation.

1. Changes in the mean volume, the rate of fatty acid and acylglycerol glycerol synthesis, the activity of lipoprotein lipase and the numbers and affinities of insulin receptors of subcutaneous adipocytes are reported for sheep at different stages of pregnancy and lactation. In addition, the serum concentrations of insulin, progesterone, prolactin, choriomammotropin, somatotropin, glucose, acetate, L-lactate, glycerol and unesterified fatty acids are reported for these sheep. 2. A switch from lipid accumulation to net lipid mobilization accompanied by a decline in the capacity for lipid synthesis, occurred at the onset of the last third of pregnancy. Net lipid mobilization continued during lactation. 3. The changes that occurred in the serum concentrations of the various hormones listed above are discussed in relation to their possible roles in the modulation of adipose tissue metabolism in sheep during pregnancy and lactation. The observations are compared with those from previous studies on the hormonal control of adipose tissue metabolism in the rat during pregnancy and lactation.     

Enzyme and protein turnover in adipose tissue in pregnancy and lactation

1. The relative rates of synthesis of fatty acid synthetase and the pyruvate dehydrogenase complex were measured in adipose tissue in virgin, late pregnant and early lactating rats after injection of l-[2,3-³H]alanine. The relative rate of synthesis of fatty acid synthetase decreased approximately 4-fold between 2 days prepartum and 2 days postpartum. The relative rate of synthesis of the pyruvate dehydrogenase complex did not change. 2. The fractional rate of total adipose tissue protein synthesis was measured by constant infusion with l-[U-¹⁴C]tyrosine. Total protein synthesis did not differ in virgin and 2-day lactating rats. The half-life of adipose tissue protein in virginn rats determined by decay of ¹⁴C label from protein after injection of NaH¹⁴CO₃ was 86.9 ± 6.7 h. This is in close agreement witht the half-life (82.5 ± 20 h) calculated from the fractional rate of protein synthesis determined by the constant infusion method.     

Adaptations in lipid metabolism of bovine adipose tissue in lactogenesis and lactation

The timing and magnitude of metabolic adaptations in adipose tissue during lactogenesis and lactation were determined in first lactation bovines. In vitro rates of lipogenesis and palmitate esterification were measured to estimate in vivo synthesis. Lipolysis was measured in the basal state and as maximally stimulated by norepinephrine or epinephrine to estimate physiological adaptations as well as the changes in catecholamine responsiveness. Subcutaneous adipose tissue was biopsied at -1, -0.5, +0.5, 1, 2, and 6 months from parturition. From 1 to 0.5 months prepartum there was a 54% reduction in lipogenesis, a 16% reduction in esterification, a 54 and 77% increase in norepinephrine- and epinephrine-stimulated free fatty acid (FFA) release, respectively, and a 28% increase in epinephrine-stimulated glycerol release. The immediate postpartum period (0.5 and 1 month) was marked by a decrease in lipogenesis to 5% and esterification to 50% of -1 month rates. During this period, norepinephrine-stimulated FFA release increased 50% above -1 month rates, epinephrine-stimulated FFA release increased 128%, and norepinephrine- and epinephrine-stimulated glycerol release increased 30 and 87%, respectively. Midlactation (2 and 6 months) was marked by a dramatic rebound in lipogenesis and esterification to 14-fold and 2.5-fold prepartum rates, respectively. Basal glycerol release doubled during this period, while basal FFA release declined to near prepartum levels. Catecholamine-stimulated FFA and glycerol release decreased from the peak during midlactation, but remained elevated compared to prepartum levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of insulin receptors in the changing metabolism of adipose tissue during pregnancy and lactation in the rat.

Changes in the volume, the rates of fatty acid synthesis and synthesis of the glycerol moiety of acylglycerols, the activity of lipoprotein lipase, and the number and affinity of insulin receptors of adipocytes, and concentrations of serum insulin, prolactin and progesterone were determined in virgin rats and in rats at various stages of pregnancy and lactation. Changes in the metabolic activities of adipose tissue appeared to be synchronized and primarily comprised a marked decrease in anabolic activity around parturition. In contrast, the number of insulin receptors (Kd 1.5 nM) per adipocyte doubled during pregnancy before returning to normal values around parturition. It is postulated that the increase in the number of insulin receptors is an adaptation to counteract the effects of insulin-antagonistic hormones during pregnancy and that the decrease in the number of receptors is primarily responsible for the loss of anabolic activity around parturition.     

Changes in brown adipose tissue lipoprotein lipase activity and lipogenesis rate during pregnancy and lactation in the rat

Brown fat lipoprotein lipase activity did not change in the first two weeks of pregnancy whereas it decreased on day 18 of gestation and was lower during late pregnancy and lactation. Fatty acid synthesis rate, measured in vivo with (3H)H2O, showed a progressive increase until day 18 of gestation followed by a decrease on day 20 of pregnancy and a reduced lipogenesis rate throughout lactation. The early reduction in the pathways of fatty acid uptake and synthesis in brown fat during the breeding cycle of the rat suggests the possibility that a decline in the substrate supply was a factor contributing to the reduced thermogenic activity of brown adipose tissue after parturition.     

Effects of early pregnancy on regional adipose tissue metabolism

Adipose tissue metabolism was studied in needle biopsies from femoral and abdominal subcutaneous depots, in 12 healthy young women, during early (9-11 weeks) pregnancy, and 6 weeks after a legal abortion. Both during pregnant and non-pregnant conditions, a higher lipoprotein lipase (LPL) activity was seen in the femoral compared to the abdominal region, but the LPL activity was not influenced by early pregnancy. Rates of fatty acid esterification and acylglyceride synthesis were not different between regions, nor affected by pregnancy. The stimulatory effect of norepinephrine (10(-7) M) on lipolysis was significantly greater in the abdominal than in the femoral region in both the pregnant and non-pregnant condition. This difference was apparently due to higher alpha-adrenergic activity in the femoral region. Pregnancy per se had no effect on lipolytic response to norepinephrine. These findings indicate that lipid accumulation is favoured in the femoral region in young women both during pregnant and non-pregnant conditions.     

Adaptations of adipose tissue metabolism and number of insulin receptors in pregnant sheep

The endocrine control of adipose tissue metabolism during pregnancy in sheep has been investigated. The number of insulin receptors of sheep adipocytes was increased during pregnancy. There was no apparent change in the concentration of serum insulin during pregnancy in sheep while the rise in serum progesterone concentration was smaller and more gradual than in rats. Net lipid deposition in adipocytes occurred during the first 55 days of pregnancy, probably due primarily to increased lipoprotein lipase activity. Net deposition of lipid had ceased by mid-pregnancy while by 125 days of pregnancy, the rate of fatty acid synthesis in adipose tissue was decreased and the serum fatty acid concentration had risen, suggesting the onset of net lipid mobilization in the tissue. Results are compared with those from other studies with rats; it would appear that different mechanisms regulate lipid deposition during pregnancy in sheep and rats.     

Adipose tissue metabolism in sheep: response to season and its modulation by reproductive state

Seasonal changes in subcutaneous adipose tissue metabolism and serum metabolite and hormone concentrations are described in virgin ewes fed a fixed amount of a cereal mixture plus hay ad libitum. Body weight, adipocyte mean cell volume, the rates of fatty acid and acylglycerol glycerol synthesis, and lipoprotein lipase activity increased from October to May and then decreased over the following five months. These changes are probably due to an increase in voluntary food intake leading to increased availability of acetate for fatty acid synthesis and also a probable rise in serum insulin concentration. Seasonal changes in adipose tissue metabolism in sheep are modulated by pregnancy and lactation, possibly mediated in part by changes in the serum insulin: growth hormone ratio. Although seasonal changes in adipose tissue metabolism are paralleled by changes in serum prolactin concentration, prolactin probably does not have a direct effect on adipose tissue metabolism.     

Integration of lipid metabolism in the mammary gland and adipose tissue by prolactin during lactation

Prolactin deficiency, induced by bromocryptine treatment, brought about reciprocal changes in the ability of adipocytes and acini isolated from lactating rats to synthesize lipids. The capacity to synthesize fatty acids and phospholipids decreased in the mammary gland and increased in adipocytes by bromocryptine treatment. In the mammary gland, the maximum potential activity of the pentose shunt as well as the specific activities of the pathway dehydrogenases were significantly reduced by bromocryptine treatment. Simultaneously, adipose tissue increased its lipogenic capacity but neither the maximum potential of the shunt nor the specific activities of the pentose phosphate shunt dehydrogenases were significantly changed with respect to the control lactating rats. Thus, a differential regulatory mechanism(s) of the pentose phosphate shunt activity appears to operate in these two tissues. Adipocytes from lactating rats showed a poor responsiveness to insulin in terms of lipid synthesis from glucose. In contrast, in adipocytes from bromocryptine treated rats insulin was able to increase lipid synthesis (105%). Sheep prolactin administration in vivo partially reversed the effects of bromocryptine. These data suggest that prolactin mediates adipocytes resistance to insulin during lactation. Phospholipid synthesis, as occurred in fatty acid synthesis, is increased in adipose tissue and decreased in mammary gland by bromocryptine treatment. However, -adrenergic stimulation increases phosphatidylinositol turnover to about the same percentages in both mammary gland acini and adipocytes from lactating rats independently of bromocryptine treatment.     

The effects of duodenal glucose and dextrin infusion on adipose tissue metabolism in sheep

Three groups of 3 sheep were penned individually and provided with pelleted dried grass. In addition two of the groups received either dextrin or glucose via duodenal cannulae. The rate of in vitro lipogenesis, from acetate of glucose, in subcutaneous adipose tissue was significantly increased in the carbohydrate-infused sheep. The increase in lipogenesis in response to glucose infusion was much greater than that to dextrin infusion. The changes in lipogenesis induced by dextrin or glucose infusion were reflected in the specific activities of the various lipogenic enzymes examined. These results are discussed in relation to the capacity of the sheep small intestine to hydrolyse alpha-linked glucose polymer.     

Enzymes of adenosine metabolism in mouse sperm suspensions

The enzymes of adenosine metabolism were investigated in suspensions of epididymal mouse spermatozoa incubated under conditions which support capacitation in vitro. High levels of adenosine deaminase activity were found in sperm suspensions, but the enzyme was located in the surrounding medium and was not intrinsic to spermatozoa. 5'-Nucleotidase was also present in the surrounding medium while in sperm cells it existed as an ecto-enzyme. Adenosine was not metabolized by washed spermatozoa under conditions used for the assay of adenosine deaminase or adenosine kinase, but it was metabolized rapidly by unwashed sperm suspensions. Incubation of sperm suspensions in conditions which modulate fertilizing ability resulted in small alterations in intrinsic 5'-nucleotidase activity of spermatozoa. In contrast, the activity of adenosine deaminase was not consistently modulated by such manipulations. Adenosine deaminase and 5'-nucleotidase exhibited similar kinetic parameters to enzymes from other sources and their activities were inhibited by coformycin and alpha, beta-methylene adenosine 5'-diphosphate, respectively. These studies highlight the low adenosine-metabolizing ability of spermatozoa coupled with the extensive metabolism in the medium which surrounds them. Extracellular adenosine metabolism can therefore occur and may modulate capacitation in vitro.     

Heredity and changes in body composition and adipose tissue metabolism after short-term exercise-training

The purpose of the experiment was to investigate the genotype dependency of body composition and adipose tissue metabolism following short-term exercise-training. Six pairs of male, sedentary monozygotic twins took part in a 22 day ergocycle training program at 58% VO2max, with a mean exercise duration of 116 min x day-1. Body weight, fat mass, percent body fat and VO2max, were evaluated before and after the training program. From a suprailiac region fat biopsy, the following adipose tissue metabolic variables were evaluated: fat cell diameter, basal and epinephrine stimulated lipolysis, basal and insulin stimulated lipogenesis from glucose and heparin releasable lipoprotein lipase activity. The exercise-training program increased (p less than 0.01) VO2max and decreased (p less than 0.01) body weight, fat mass and percent body fat. Variation in response within twin pairs was not significantly different than response between pairs in the aforementioned variables. However, a significant within pair resemblance (p less than 0.01) for changes in fat free mass was observed. Adipose tissue metabolic indicators exhibited a large interindividual variation in response to exercise-training. Significant within twin pair resemblance was observed only for basal lipogenesis. Moreover, the non significant within twin pair resemblance for changes in body fat and adipose tissue metabolic indicators suggests that heredity is not a major factor influencing changes in body fat and adipose tissue indicators to short-term training resulting in negative energy balance. Changes in fat free mass were, however, closely coupled to the genotype.     

Properties of pyruvate dehydrogenase of rat mammary tissue and its changes during pregnancy, lactation and weaning

1. At 30min after oral administration unchanged Synacthen [corticotrophin-(1-24)-tetracosapeptide] was found in the stomach but could not be detected in the lumen of the small intestine of the rat. 2. Synacthen and 41795-Ba {[d-Ser(1), Lys(17), Lys(18)]corticotrophin-(1-18)-octadecapeptide amide} were rapidly metabolized in vitro by both intestinal juice and everted pieces of small intestine. Peptide products were not found either in the intestinal tissue or in the fluid bathing the serosal tissue. 3. Glucose but not O(2) was necessary for the breakdown of the two adrenocorticotrophin analogues by everted tissue. 4. When the products obtained after partial digestion were chromatographically separated and identified, a pattern of breakdown emerged. The N-terminus of Synacthen and the Phe(7)-Arg(8) bond in both analogues were particularly labile. The d-serine N-terminal residue of 41795-Ba conferred a marked protection to aminopeptidase action. 5. The relative susceptibilities of peptide bonds would have been difficult to predict on the basis of existing knowledge of the properties of enzymes of the small intestine.