Glyceride-glycerol Synthesis Research Articles

Insulin signaling requires glucose to promote lipid anabolism in adipocytes

Adipose tissue is essential for metabolic homeostasis, balancing lipid storage and mobilization based on nutritional status. This is coordinated by insulin, which triggers kinase signaling cascades to modulate numerous metabolic proteins, leading to increased glucose uptake and anabolic processes like lipogenesis. Given recent evidence that glucose is dispensable for adipocyte respiration, we sought to test whether glucose is necessary for insulin-stimulated anabolism. Examining lipogenesis in cultured adipocytes, glucose was essential for insulin to stimulate the synthesis of fatty acids and glyceride-glycerol. Importantly, glucose was dispensable for lipogenesis in the absence of insulin, suggesting that distinct carbon sources are used with or without insulin. Metabolic tracing studies revealed that glucose was required for insulin to stimulate pathways providing carbon substrate, NADPH, and glycerol 3-phosphate for lipid synthesis and storage. Glucose also displaced leucine as a lipogenic substrate and was necessary to suppress fatty acid oxidation. Together, glucose provided substrates and metabolic control for insulin to promote lipogenesis in adipocytes. This contrasted with the suppression of lipolysis by insulin signaling, which occurred independently of glucose. Given previous observations that signal transduction acts primarily before glucose uptake in adipocytes, these data are consistent with a model whereby insulin initially utilizes protein phosphorylation to stimulate lipid anabolism, which is sustained by subsequent glucose metabolism. Consequently, lipid abundance was sensitive to glucose availability, both during adipogenesis and in Drosophila flies in vivo Together, these data highlight the importance of glucose metabolism to support insulin action, providing a complementary regulatory mechanism to signal transduction to stimulate adipose anabolism.

Activation of adipose tissue glycerokinase contributes to increased white adipose tissue mass in mice fed a high-fat diet.

Investigate the pathways of glycerol-3-P (G3P) generation for triacylglycerol (TAG) synthesis in retroperitoneal (RWAT) and epididymal (EWAT) white adipose tissues from high-fat diet (HFD)-fed mice. Mice were fed for 8 weeks a HFD and glycolysis, glyceroneogenesis and direct phosphorylation of glycerol were evaluated, respectively, by 2-deoxyglucose uptake, phosphoenolpyruvate carboxykinase (PEPCK-C) activity and pyruvate incorporation into TAG-glycerol, and glycerokinase activity and glycerol incorporation into TAG-glycerol in both tissues. HFD increased body and adipose tissue mass and serum levels of glucose and insulin, which were accompanied by glucose intolerance. RWAT and EWAT from HFD-fed mice had increased rates of de novo fatty acid (FA) synthesis (52% and 255%, respectively). HFD increased lipoprotein lipase (LPL) activity and content in EWAT (107%), but decreased in RWAT (79%). HFD decreased the lipolytic response to norepinephrine (57%, RWAT and 25%, EWAT), β3-adrenoceptor content (50%), which was accompanied by a decrease in phosphorylated-hormone-sensitive lipase (~80%) and phosphorylated-adipocyte triacylglycerol lipase (~60%) in both tissues. HFD decreased the in vitro rates of glucose uptake (3.5- and 6-fold), as well as in glyceride-glycerol synthesis from pyruvate (~3.5-fold) without changes in PEPCK-C activity and content in RWAT and EWAT, but increased glycerokinase activity(~3-fold) and content (90 and 40%) in both tissues. The data suggest that direct phosphorylation of glycerol by glycerokinase may be responsible for maintaining the supply of G3P for the existing rates of FA esterification and TAG synthesis in RWAT and EWAT from HFD-fed mice, contributing, along with a lower lipolytic response to norepinephrine, to higher adiposity.

Increased Glyceride–Glycerol Synthesis in Liver and Brown Adipose Tissue of Rat: In‐Vivo Contribution of Glycolysis and Glyceroneogenesis

We have previously shown that a high-protein, carbohydrate-free diet can decrease the production of glycerol-3-phosphate (G3P) from glucose and increase glyceroneogenesis in both brown (BAT) and epididymal (EAT) adipose tissue. Here, we utilized an in-vivo approach to examine the hypothesis that there is reciprocal regulation in the G3P synthesis from glucose (via glycolysis) and glyceroneogenesis in BAT, EAT and liver of fasted rats and cafeteria diet-fed rats. Glyceroneogenesis played a prominent role in the generation of G3P in the liver (~70%) as well as in BAT and EAT (~80%) in controls rats. The cafeteria diet induced an increase in the total glyceride-glycerol synthesis and G3P synthesis from glucose and a decrease in glyceroneogenesis in BAT; this diet did not affect either the total glyceride-glycerol synthesis or G3P generation from glyceroneogenesis or glycolysis in the liver or EAT. Fasting induced an increase in total glyceride-glycerol synthesis and glyceroneogenesis and a decrease in G3P synthesis from glucose in the liver but did not affect either the total glyceride-glycerol synthesis or G3P synthesis from glyceroneogenesis in BAT and EAT, despite a reduction in glycolysis in these tissues. These data demonstrate that reciprocal changes in the G3P generation from glucose and from glyceroneogenesis in the rat liver and BAT occur only when the synthesis of glycerides-glycerol is increased. Further, our data suggest that this increase may be essential for the systemic recycling of fatty acids by the liver from fasted rats and for the maintenance of the thermogenic capacity of BAT from cafeteria diet-fed rats.

Enhanced utilization of glycerol for glyceride synthesis in isolated adipocytes from early pregnant rats

Adipose tissue normally has low glycerol kinase activity, but its expression is enhanced under conditions of augmented insulin sensitivity and/or obesity. Since these conditions occur during early pregnancy, the comparative utilization of glucose or glycerol by isolated adipocytes from rats at 0, 7, 14, or 20 days of pregnancy was studied. Incubations were carried out in the presence of [U(14)C]-glucose or -glycerol in medium supplemented or not with 5 mM glucose and 100 nM insulin. The conversion of glucose into esterified fatty acids and glyceride glycerol was greatest in adipocytes from 7-day pregnant rats, the effect being further enhanced by insulin. Both the amount of aquoporin 7 and the in vitro conversion of glycerol into glyceride glycerol were greatest in adipocytes of 7-day pregnant rats, the later being unaltered by insulin. In the presence of glucose, the overall glycerol utilization was lower than in its absence and glycerol conversion into glyceride glycerol was further decreased by insulin, the effect only being significant in adipocytes from 7-day pregnant rats. It is proposed that the enhanced utilization of glycerol for glyceride glycerol synthesis in adipose tissue contributes to the net accumulation of fat depots that normally takes place in early pregnancy.

Glyceroneogenesis and the supply of glycerol-3-phosphate for glyceride-glycerol synthesis in liver slices of fasted and diabetic rats

The pathways of glycerol-3-phosphate (G3P) generation for glyceride synthesis were examined in precision-cut liver slices of fasted and diabetic rats. The incorporation of 5 mM [U-(14)C]glucose into glyceride-glycerol, used to evaluate G3P generation via glycolysis, was reduced by approximately 26-36% in liver slices of fasted and diabetic rats. The glycolytic flux was reduced by approximately 60% in both groups. The incorporation of 1.0 mM [2-(14)C]pyruvate into glyceride-glycerol (glyceroneogenesis) increased approximately 50% and approximately 36% in slices of fasted and diabetic rats, respectively, which also showed a two-fold increase in the activity phosphoenolpyruvate carboxykinase. The increased incorporation of 1.0 mM [2-(14)C]pyruvate into glyceride-glycerol by slices of fasted rats was not affected by the addition of 5 mM glucose to the incubation medium. The activity of glycerokinase and the incorporation of 1 mM [U-(14)C]glycerol into glyceride-glycerol, evaluators of G3P formation by direct glycerol phosphorylation, did not differ significantly from controls in slices of the two experimental groups. Rates of incorporation of 1 mM [2-(14)C]pyruvate and [U-(14)C]glycerol into glucose of incubation medium (gluconeogenesis) were approximately 140 and approximately 20% higher in fasted and diabetic slices than in control slices. It could be estimated that glyceroneogenesis by liver slices of fasted rats contributed with approximately 20% of G3P generated for glyceride-glycerol synthesis, the glycolytic pathway with approximately 5%, and direct phosphorylation of glycerol by glycerokinase with approximately 75%. Pyruvate contributed with 54% and glycerol with 46% of gluconeogenesis. The present data indicate that glyceroneogenesis has a significant participation in the generation of G3P needed for the increased glyceride-glycerol synthesis in liver during fasting and diabetes.

Glyceroneogenesis and the Source of Glycerol for Hepatic Triacylglycerol Synthesis in Humans

Glyceroneogenesis, i.e. the synthesis of the glycerol moiety of triacylglycerol from pyruvate, has been suggested to be quantitatively important in both the liver and adipose tissue during fasting. However, the actual contribution of glyceroneogenesis to triacylglycerol synthesis has not been quantified in vivo in human studies. In the present study we have measured the contribution of glycerol and pyruvate to in vivo synthesis of hepatic triacylglycerol in nonpregnant and pregnant women after an overnight fast. Five nonpregnant women were administered [(13)C(3)]glycerol tracer as prime constant rate infusion, and the appearance of tracer in plasma glucose and triacylglycerol was quantified using gas chromatography-mass spectrometry. The contribution of pyruvate to hepatic triacylglycerol was quantified in nonpregnant and pregnant women using the deuterium labeling of body water method. The appearance of [(2)H] in hydrogens on C(1) and C(3) of triacylglycerol was measured following periodate oxidation of the glycerol isolated from hydrolyzed triacylglycerol. After a 16-h fast, approximately 6.1% of the plasma triacylglycerol pool was derived from plasma glycerol, whereas 10 to 60% was derived from pyruvate in nonpregnant women and pregnant women early in gestation. Our data suggest that glyceroneogenesis from pyruvate is quantitatively a major contributor to plasma triacylglycerol synthesis and may be important for the regulation of very low density lipoprotein triacylglycerol production. Our data also suggest that 3-glycerol phosphate is in rapid equilibrium with the triosephosphate pool, resulting in rapid labeling of the triose pool by the administered tracer glycerol. Because the rate of flux of triosephosphate to glucose during fasting far exceeds that to triacylglycerol, more glycerol ends up in glucose than in triacylglycerol. Alternatively, there may be two distinct pools of 3-glycerol phosphate in the liver, one involved in generating triosephosphate from glycerol and the other involved in glyceride-glycerol synthesis.

Glucose contribution to in vivo synthesis of glyceride-glycerol and fatty acids in rats adapted to a high-protein, carbohydrate-free diet.

Triacylglycerol (TAG) synthesis from all carbon sources and from glucose carbon was evaluated in rats fed a high-protein, carbohydrate-free (HP) diet or control diet by determining simultaneously in the same animal the rate of incorporation of 3H2O and of 14C-glucose into the two TAG moieties in the carcass, liver, and retroperitoneal and epididymal adipose tissue. Incorporation rates of 3H2O into TAG-fatty acids (FAs) in the two adipose tissues and in liver were reduced in HP rats to about 20% and 50%, respectively, of the rates in control rats. In the two experimental groups, glucose was a poor precursor for FA synthesis, contributing only 22.8% of whole-body (carcass plus liver) total FA synthesis in control rats and even less (14%) in HP rats. In contrast to the reduction in FA synthesis, incorporation of 3H2O into TAG-glycerol in HP rats did not differ significantly or was even higher (in epididymal tissue) versus the control level. In all tissues of both HP and control rats, the rate of 14C-glucose incorporation into TAG-glycerol was much higher than the rate of incorporation into FA. Glyceroneogenesis, estimated by subtracting TAG-glycerol synthesis from glucose from the rate obtained with 3H2O, was significantly increased in adipose tissue from HP rats, with almost all of the glycerol formed by this route being used to esterify preformed FAs. It is suggested that the increased adipose tissue glyceroneogenesis is important for esterification of diet-derived FA and preservation of body fat stores in rats adapted to the HP diet.

Effects of prolonged treatment of lactating goats with bovine somatotropin on aspects of adipose tissue and liver metabolism

The effects of prolonged (22 weeks) treatment of lactating goats with bovine somatotropin on the metabolism of adipose tissue and liver has been investigated. Somatotropin treatment resulted in smaller adipocytes, decreased rate of fatty acid synthesis and decreased total acetyl-CoA carboxylase activity of adipocytes, but with no change in the proportion of this enzyme in the active state. The rate of acylglycerol glycerol synthesis from glucose of adipocytes tended to decrease as did total glucose utilization by the tissue. Glucose conversion to lactate was unchanged by somatotropin treatment but glucose conversion to other products was decreased. Maximum response of adipose tissue to insulin was unchanged but the sensitivity to insulin decreased on somatotropin treatment. Treatment with somatotropin had no effect on basal lipolysis and decreased maximum response to the beta-agonist isoproterenol, but this probably reflects the rate of isoproterenol-stimulated lipolysis varying with cell volume in adipocytes. No apparent change in response either to alpha 2-adrenergic agonists or to adenosine was apparent. The number of beta-adrenergic receptors was unchanged in adipocyte membranes but the number of alpha 2-adrenergic receptors increased. The rate of hepatic gluconeogenesis in vitro, the activity of key gluconeogenic enzymes and the modulation of the rate of gluconeogenesis by butyrate were unchanged except for the effect of this latter agent on gluconeogenesis from propionate. Hepatic ketogenic activity, as indicated by the activity of carnitine palmitoyl-CoA-transferase-1 and the concentrations of carnitine and acyl carnitines, was unchanged by treatment. Thus at the end of a prolonged period of treatment with somatotropin in lactating goats, lipid synthesis in adipose tissue is still decreased but no effects on liver lipid and carbohydrate metabolism were apparent.

Circulating metabolite utilization by periuterine adipose tissue in situ in the pregnant rat

To study the use of glucose for lipid synthesis by the periuterine adipose tissue in situ, 14C-glucose was infused through the left uterine artery of anesthetized, fed pregnant and virgin control rats. A greater amount of 14C-lipid always appeared in the adipose tissue from the left uterine horn than in the tissue from the right uterine horn, indicating direct utilization of the infused 14C-glucose by the tissue. Glucose utilization for both glyceride glycerol and fatty acid synthesis increased from day 0 (virgin rats) to day 20 of gestation and then decreased dramatically on day 21. In virgin and 12-day pregnant rats, glucose was incorporated into either lipidic moiety at similar rates, whereas in late pregnant rats glucose utilization for glyceride glycerol synthesis was four to five times greater than for fatty acids. The utilization of circulating fatty acids and the lipoprotein triglyceride-derived fatty acids was studied by infusing 14C-palmitate or 14C-triolein-labeled very-low-density lipoprotein (VLDL) through the left uterine artery in both virgin and 20-day pregant rats. Incorporation of fatty acids from either one of these plasma sources was significantly higher in the pregnant than in virgin rats. This high amount of fatty acid acquisition did not account for the very active glyceride glycerol synthesis observed in pregnant rats and can only be explained by the intracellular reesterification of some lipolitic fatty acids. The results suggest a highly accelerated triacylglycerol/fatty acid substrate cycle in adipose tissue during late pregnancy, which would allow active esterification (contributing to fat accumulation) and responsive lipolysis (permitting rapid fat mobilization) by the mother.

Effect of Diet and Substrate on the In Vitro Measurement of Cholesterol and Fatty-Acid Synthesis in Hepatic Tissue of Japanese Quail

A comparison of acetate, glucose, mevalonate, or water as radioactive substrates for the hepatic synthesis of cholesterol, fatty acids, and glyceride-glycerol was made in Japanese quail fed diets containing either beef fat or tuna oil. The quail fed a diet containing beef fat were fatter and had a significantly higher (P<.01) concentration of serum cholesterol (5.6 mM per L) than that measured in the serum of quail given tuna oil (4.1 mM per L). Both in vitro cholesterol and fatty-acid synthesis were greater in the quail fed a diet of beef fat than in those fed a diet containing tuna oil. The results showed that mevalonate was the most-suitable radioactive substrate for measuring cholesterol synthesis, whereas glucose was the most-suitable radioactive substrate for measuring fatty-acid and glyceride-glycerol synthesis.

Adrenergic blockade paradoxically increases lipogenic response of brown adipose tissue to sympathetic nerve stimulation

Intermittent electrical stimulation of sympathetic nerves entering the interscapular brown adipose tissue (BAT) in rats increased the rate of glyceride glycerol synthesis in BAT but the fatty acid synthesis did not change. Simultaneous administration of phenoxybenzamine and propranolol paradoxically increased the fatty acid synthesis in response to the nerve stimulation whereas the glyceride glycerol synthesis was inhibited. Propranolol alone was also effective in mimicking the effects of adrenergic blockade, but guanethidine selectively eliminated the lipogenic response to the nerve stimulation. These results indicate that synthesis of glyceride glycerol induced by sympathetic nerve stimulation is largely due to β-adrenergic action of noradrenaline, whereas synthesis of fatty acids may be mediated by non-adrenergic transmission of the sympathetic nerves.

Some aspects of metabolic adaptations in lipid metabolism during starvation are mimicked by epinephrine in rat adipocytes

1. 1. The effects of fasting on the neutral lipid synthesis to insulin and/or epinephrine in isolated fat cells have been examined using [l- 14C]acetate and [l- 14C]glucose. 2. 2. The ability of adipocytes from starved rats to synthesize fatty acids from both labeled substrates was markedly diminished compared to adipocytes from control rats. 3. 3. The response of lipogenic stimulation to insulin at all concentrations tested was greatly diminished in adipocytes from 24 hr starved rats. 4. 4. [l- 14C]glucose utilization rates in the absence or in the presence of insulin were not significantly different in adipocytes from 24 hr starved rats as compared with control adipocytes, although basal and insulin stimulated glyceride-glycerol synthesis were significantly higher in starved adipocytes. 5. 5. Epinephrine acutely inhibited [l- 14C]acetate incorporation into fatty acids for insulin-stimulated lipogenesis in control adipocytes, in contrast, this lipolytic agent strongly increased [l- 14C]glucose conversion to triacyglycerols. 6. 6. In both cases, the differences in lipid synthesis capacities found in both nutritional states were abolished by epinephrine.

Antilipogenic but not lipolytic effects of recombinant DNA-derived bovine somatotropin treatment on ovine adipose tissue; variation with genetic type

1. 1. Lambs from three breeds (East Friesland, Oxford and Texel) were treated with recombinant DNA-derived bovine somatotropin (BST) at 0.05, 0.10, 0.20 mg/kg per day and fat metabolism assessed in subcutaneous adipose tissue biopsy samples. 2. 2. BST treatment decreased adipose cell volume, fatty acid synthesis and acylglycerol glycerol synthesis but did not alter lipolytic rates (basal or noradrenaline-stimulated). 3. 3. Genetic type influenced metabolism in a number of ways, most notably East Friesland lambs had lower fatty acid esterification rates and responded poorly to BST in terms of reduced lipogenesis as compared to the Oxford and Texel lambs. 4. 4. Blood urea concentration was decreased by BST treatment suggesting increased nitrogen retention. 5. 5. These results emphasise the role of somatotropin as an inhibitor of adipose tissue lipogenesis but cast further doubt on a physiological role in regulating lipolysis.

Rapid effects of insulin and glucose on the hepatic incorporation of gluconeogenic substrates into glyceride glycerol and glycogen

1. 1. The hepatic utilization of gluconeogenic substrates was investigated shortly after portal infusion of either insulin or glucose in fasted rats. 2. 2. After 20 min of insulin infusion blood glucose concentration decreased. However, neither glucose generation from precursors such as alanine or pyruvate nor their incorporation into fatty acids was modified. Under these conditions, insulin rapidly increased the incorporation of gluconeogenic substrates into the hepatic glyceride glycerol fraction. Insulin treatment led to a decrease in substrate incorporation into liver glycogen. 3. 3. After 20 min of portal glucose infusion both plasma insulin and glucose concentrations increased and the incorporation of pyruvate into hepatic glyceride glycerol and into glycogen was also stimulated. 4. 4. A close relationship was observed between blood glucose concentrations and the level of incorporation of gluconeogenic substrates into liver glycogen. 5. 5. In conclusion, during fasting insulin stimulates the incorporation of gluconeogenic substrates into the glycerol moiety of hepatic glycerides, which may be the preferential mechanism through which fatty acid esterification is accomplished during refeeding. This effect of insulin is rapid and detected even before other classical modifications induced by the hormone such as gluconeogenesis inhibition or lipogenesis activation. Furthermore, the effect is not related to insulin-induced hypoglycemia since glucose infusion mimics insulin action on glyceride glycerol synthesis.

Genetic variations in subcutaneous adipose tissue metabolism in sheep

ABSTRACTAdipocyte volume rates of fatty acid synthesis, acylglycerol glycerol synthesis and lipolysis (basal and noradrenaline stimulated) along with the activities of acetyl CoA carboxylase and lipoprotein lipase were determined in subcutaneous adipose tissue, sampled by biopsy, from the rump of four breeds of sheep differing in growth and body characteristics.Significant differences among breeds were observed for adipocyte volume, fatty acid synthesis, stimulated lipolysis rates, initial and total acetyl CoA carboxylase activity and lipoprotein lipase activity, but not for acylglycerol glycerol synthesis.Differences in adipocyte volume did not appear to be related to the previously reported carcass fatnesses of the breeds. Similarly differences in adipocyte volume were not related to differences in either de novo fatty acid synthesis or lipolysis rates. Across breeds there was a trend toward higher acylglycerol glycerol synthesis rates associated with greater adipocyte volume although the source of fatty acids for esterification varied greatly.Breed variation in fatness in sheep therefore appears to be a consequence of different balances of anabolic and catabolic processes in adipose tissue, with a unique pattern for each breed. Further elucidation of these patterns may lead to the identification of key sites for genetic manipulation. In addition these breed differences provide an alternative, complementary and qualitatively different, model for the study of the control of fat metabolism to that provided by nutritional or hormonal manipulations.

Insulin receptor and postbinding defects in KK mouse adipocytes and improvement by ciglitazone

Alterations of the insulin receptor and of glucose metabolism were examined in adipocytes from genetically diabetic KK mice. Compared with those from control C57BL/6 mice, adipocytes from KK mice showed weaker insulin binding and were less sensitive and less responsive to insulin with respect to 3-O-methylglucose uptake and [1-14C]glucose oxidation. However, insulin had no difference in effect between the two groups of mice with respect to [6-14C]glucose oxidation, glyceride-glycerol synthesis, or fatty acid synthesis from [1-14C]- and [6-14C]glucose. [1-14C]Glucose oxidation of KK cells was also insensitive to insulin mimics such as vitamin K5 and H2O2. When adipose tissues were precultured with insulin or insulin mimics for 24 h, adipocytes from C57BL/6 mice showed decreased insulin binding, but KK cells did not. When administered orally to KK mice for 2 weeks, ciglitazone made adipocytes more sensitive to insulin, more responsive to insulin with respect to glucose uptake and oxidation, and more capable of binding insulin. Impairment of the downregulation at the insulin receptor caused by exposure to insulin or insulin mimics was normalized by ciglitazone treatment in KK cells. In conclusion, KK cells are insulin-resistant due to defects of the insulin receptor and postbinding system in the glucose uptake and pentose pathways. In addition, regulation of the insulin receptor seems to be closely related to the postbinding system.

Utilization of glucose, alanine, lactate, and glycerol as lipogenic substrates by periuterine adipose tissue in situ in fed and starved rats.

A technique previously used to study placental transfer in pregnant rats, consisting of labeled tracer infusion through the left uterine artery, was employed to determine the utilization of lipogenic substrates by periuterine adipose tissue in the fed and 48-hr starved female virgin rat. After 20 min infusion with either D[U-14C]glucose, L-[U-14C]alanine, [U-14C]glycerol or L-[U-14C]lactate, the radioactivity appearing in periuterine adipose tissue 14C-labeled lipids from the left side was always higher than that appearing in tissue from the right side. Negligible radioactivity was detected in the tissue from either side when the infusion was done with non-metabolizable derivatives such as L-[1-14C]glucose or [1-14C]alpha-aminoisobutyric acid. Simultaneous infusion of L-[U-14C]alanine and an alanine transaminase inhibitor (aminooxyacetic acid) into the left uterine artery completely blocked the conversion of the alanine transaminase inhibitor (aminooxyacetic acid) into the left uterine artery completely blocked the conversion of the alanine into periuterine adipose tissue 14C-labeled lipids. The utilization of the infused substrate for fatty acids and glyceride-glycerol synthesis by the tissue was quantified by taking into account the infused radioactivity, the difference in the amount of 14C-labeled lipids appearing in periuterine adipose tissue on the left and the right sides, the arterial plasma concentration of the studied metabolite, and the uterine horn blood flow. In fed animals, the highest fatty acid synthesis was found with lactate, followed by glucose, alanine, and glycerol. This process was intensely decreased with all the substrates in 48-hr starved rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Glucose, acetate, and lactate metabolism in perirenal adipose tissue of fetal and newborn calves.

Rates of utilization of glucose, acetate, and lactate and activities of selected enzymes were determined in vitro to characterize the nature of lipogenesis and metabolite utilization in perirenal adipose tissue from 6- to 7-month old fetal and 3- to 4-h-old unsuckled newborn calves. Contribution of the pentose phosphate cycle to glucose metabolism was estimated using specifically labeled glucose. Rates of fatty acid synthesis from all three substrates and oxidation of glucose were much greater in fetal than in newborn adipose tissue. In fetal adipose tissue, acetate and lactate were major sources of carbon for fatty acid synthesis; glucose functioned mainly by metabolism via the pentose phosphate cycle to provide reducing equivalents for fatty acid synthesis and by incorporation into glyceride glycerol for fatty acid esterification. Pentose phosphate cycle contributed 58 and 12% to glucose metabolism in adipose tissue of fetal and newborn calves, respectively. Adipose tissue metabolism of newborn calves was characterized by greatly depressed rates of fatty acid synthesis despite high enzyme activities and elevated rates of glyceride glycerol synthesis.

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.

Comparative utilization of glycerol and alanine as liver gluconeogenic substrates in the fed late pregnant rat

1. 1. The appearance of plasma [ 14C]glucose in the inferior cava vein after a pulse of 0.2 mmol of [U- 14C] l-alanine or [U- 14C]glycerol/200 g body wt given through the portal vein was studied in fed 21 day pregnant rats and virgin controls under pentobarbital anesthesia. In both groups value were much higher when [U- 14C]glycerol was the administered tracer than when [U- 14C] l-alanine, and they were augmented in pregnant versus virgin animals at 1 min where receiving [U- 14C]glycerol and at 2 min when receiving [U- 14C] l-alanine. 2. 2. 20 min after the tracers rats receiving [U- 14C]glycerol showed much higher liver [ 14C]glycogen and [ 14]glyceride glycerol than those receiving [U- 14C] pl-lanamine. Radioactivity present in liver as [ 14C]glyceride glycerol was greater in pregnant than in virgin rats receiving [U- 14C]glycerol whereas radioactivity corresponding to [ 14C]fatty acids was lower in the former group receiving either tracer. 3. 3. At 20 min after maternal treatments fetuses showed lower plasma [ 14C]alanine values but plasma [ 14C]glucose and liver [ 14]glycogen values were much greater in featuses from mothers receiving [U- 14C]glycerol than [U- 14C] l-alanine. 4. 4. Besides showing the higher gluconeogenic efficiency in pregnant than in virgin rats, results indicate that at late gestation glycerol is used as a preferntial substrate for both glucose and glyceride glycerol synthesis in liver.