Effect of the beta-adrenoblocker propranolol on adrenaline-stimulated lipolysis in the adipose tissue of spontaneously hypertensive rats

The effect of the beta-adrenoblocker propranolol on adrenaline-stimulated lipolysis was studied in the adipose tissue of spontaneously hypertensive rats (SHR) and control rats. The lipolytic activity was estimated from the increase in glycerol concentration in the incubation medium in vitro. The adipose tissue of SHR responded to adrenaline similarly to that of control rats, but the concentration of adrenaline inducing the half-maximum response (KA) was 2 times less for SHR than KA for normotensive controls. Under propranolol effect this parameter was increased more significantly in SHR than in controls. These data indicate higher sensitivity of SHR adipose tissue to propranolol that may well be relative to alteration of the properties of beta-adrenergic receptors of adipose tissue in this form of hypertension.     

Epinephrine induces PDK4 mRNA expression in adipose tissue from obese, insulin resistant rats

Thiazolidinediones (TZDs) are a commonly prescribed class of insulin sensitizing drugs that increase fatty acid re-esterification, in part through the induction of pyruvate dehydrogenase kinase 4 (PDK4). Owing to the deleterious side effects of TZDs the identification of alternative approaches with which to increase PDK4 is essential. We recently demonstrated that epinephrine increases PDK4 expression through p38 and peroxisome proliferator-activated receptor γ (PPARγ) dependent pathways in cultured adipose tissue from lean rats. The purpose of this study was to determine whether acute epinephrine treatment, in vivo, can induce PDK4 mRNA expression in adipose tissue from obese, insulin resistant rats and if the reputed signaling pathways mediating this effect are intact. To this end we fed male Wistar rats a chow or high-fat diet (HFD, 60% kcals from fat) for 6 weeks. Rats were then injected with a weight-adjusted bolus of epinephrine and tissue harvested. Despite a blunted activation of p38 epinephrine increased PDK4 mRNA expression to a similar extent in adipose tissue from chow and HFD rats. 5'AMP-activated protein kinase (AMPK) signaling was not altered by the HFD. Similar to epinephrine, 2 h of swim exercise, an intervention that increases plasma catecholamines, also increased PDK4 mRNA levels to a similar extent in adipose tissue from both lean and HFD rats. Collectively these findings demonstrate, for the first time, that acute elevations in catecholamines induce PDK4 in adipose tissue from HFD rats, that this effect is likely independent of p38, a reputed mediator of PDK4 expression and that exercise, similar to TZDs can induce PDK4 in adipose tissue from obese, insulin resistant rats.     

Regulation of adipose-tissue pyruvate dehydrogenase by insulin and other hormones

1. In epididymal adipose tissue synthesizing fatty acids from fructose in vitro, addition of insulin led to a moderate increase in fructose uptake, to a considerable increase in the flow of fructose carbon atoms to fatty acid, to a decrease in the steady-state concentration of lactate and pyruvate in the medium, and to net uptake of lactate and pyruvate from the medium. It is concluded that insulin accelerates a step in the span pyruvate-->fatty acid. 2. Mitochondria prepared from fat-cells exposed to insulin put out more citrate than non-insulin-treated controls under conditions where the oxaloacetate moiety of citrate was formed from pyruvate by pyruvate carboxylase and under conditions where it was formed from malate. This suggested that insulin treatment of fat-cells led to persistent activation of pyruvate dehydrogenase. 3. Insulin treatment of epididymal fat-pads in vitro increased the activity of pyruvate dehydrogenase measured in extracts of the tissue even in the absence of added substrate; the activities of pyruvate carboxylase, citrate synthase, glutamate dehydrogenase, acetyl-CoA carboxylase, NADP-malate dehydrogenase and NAD-malate dehydrogenase were not changed by insulin. 4. The effect of insulin on pyruvate dehydrogenase activity was inhibited by adrenaline, adrenocorticotrophic hormone and dibutyryl cyclic AMP (6-N,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate). The effect of insulin was not reproduced by prostaglandin E(1), which like insulin may lower the tissue concentration of cyclic AMP (adenosine 3':5'-cyclic monophosphate) and inhibit lipolysis. 5. Adipose tissue pyruvate dehydrogenase in extracts of mitochondria is almost totally inactivated by incubation with ATP and can then be reactivated by incubation with 10mm-Mg(2+). In this respect its properties are similar to that of pyruvate dehydrogenase from heart and kidney where evidence has been given that inactivation and activation are catalysed by an ATP-dependent kinase and a Mg(2+)-dependent phosphatase. Evidence is given that insulin may act by increasing the proportion of active (dephosphorylated) pyruvate dehydrogenase. 6. Cyclic AMP could not be shown to influence the activity of pyruvate dehydrogenase in mitochondria under various conditions of incubation. 7. These results are discussed in relation to the control of fatty acid synthesis in adipose tissue and the role of cyclic AMP in mediating the effects of insulin on pyruvate dehydrogenase.     

Lipolytic response of fat cells to catecholamines in sedentary and exercise-trained women

It has been shown that adipose tissue lipolytic activity is increased in endurance-trained subjects. In women, adipose tissue is extensive and it was thought interesting to confirm that endurance training increases the capacity of female adipose tissue to mobilize lipids, and moreover to more fully understand the mechanisms involved. So, biopsies of fat were obtained from the periumbilical region of 13 trained female runners (T) and 17 sedentary women (S) and the in vitro response to catecholamines of the collagenase-isolated fat cells was studied. Glycerol release, chosen as adipocyte lipolysis indicator, was measured by bioluminescence for various epinephrine and norepinephrine concentrations. In both groups, these substances provoked an increase in lipolysis, but the response was significantly higher in T. In both groups, isoproterenol increased the lipolytic activity above basal concentrations at 10(-8) M and above. Lipolytic activity in T was significantly higher (P less than 0.01) than the S control at 10(-7) M and above. Epinephrine plus propranolol decreased lipolysis in both groups, but at 10(-5) M, lipolytic activity was significantly lower in S than in T (P less than 0.05). It is concluded that in female subjects, endurance training increases the sensitivity of subcutaneous abdominal adipose tissue to the lipolytic action of catecholamines; this effect seems to be related both to a decreased efficiency of the alpha 2-adrenergic pathway and to an increased efficiency of the beta-adrenergic pathway. This latter effect seems to take place at a step beyond the receptor-adenylate cyclase system in the lipolytic cascade.     

Specific expression of lactase in the jejunum and colon during postnatal development and hormone treatments in the rat.

The effects of hyperinsulinaemia imposed on normal rats on the subsequent insulin-responsiveness in vivo of 2-deoxy-D-glucose uptake of white adipose tissue and of various muscle types were investigated. This was done by treating normal rats with insulin via osmotic minipumps, and by comparing them with saline-infused controls. Hyperinsulinaemia produced by prior insulin treatment resulted in a well-tolerated hypoglycaemia. At the end of the treatment, the glucose utilization index of individual tissues was determined by euglycaemic/hyperinsulinaemic clamps associated with the labelled 2-deoxy-D-glucose method. Prior insulin treatment resulted in increased insulin-responsiveness of the glucose utilization index of white adipose tissue, and in increased total lipogenesis in white adipose tissue and fat-pad weight. In contrast, prior insulin treatment resulted in a decreased glucose utilization index of several muscles. These opposite effects of hyperinsulinaemia on glucose utilization in white adipose tissue and muscles persisted when the hypoglycaemia-induced catecholamine output was prevented (adrenomedullectomy, propranolol treatment), as well as when hypoglycaemia was normalized by concomitant insulin treatment and glucose infusion. Insulin suppressed hepatic glucose production during the clamps in insulin-treated rats as in the respective controls, whereas total hepatic lipid synthesis and liver fat content were greater in rats treated with insulin than in controls. It is concluded that hyperinsulinaemia itself could be one of the driving forces responsible for producing increased glucose utilization by white adipose tissue, increased total lipid synthesis with fat accumulation in adipose tissue and the liver, together with an insulin-resistant state at the muscular level.     

Adrenaline is a critical mediator of acute exercise-induced AMP-activated protein kinase activation in adipocytes

Exercise increases AMPK (AMP-activated protein kinase) activity in human and rat adipocytes, but the underlying molecular mechanisms and functional consequences of this activation are not known. Since adrenaline (epinephrine) concentrations increase with exercise, in the present study we hypothesized that adrenaline activates AMPK in adipocytes. We show that a single bout of exercise increases AMPKalpha1 and alpha2 activities and ACC (acetyl-CoA carboxylase) Ser79 phosphorylation in rat adipocytes. Similarly to exercise, adrenaline treatment in vivo increased AMPK activities and ACC phosphorylation. Pre-treatment of rats with the beta-blocker propranolol fully blocked exercise-induced AMPK activation. Increased AMPK activity with exercise and adrenaline treatment in vivo was accompanied by an increased AMP/ATP ratio. Adrenaline incubation of isolated adipocytes also increased the AMP/ATP ratio and AMPK activities, an effect blocked by propranolol. Adrenaline incubation increased lipolysis in isolated adipocytes, and Compound C, an AMPK inhibitor, attenuated this effect. Finally, a potential role for AMPK in the decreased adiposity associated with chronic exercise was suggested by marked increases in AMPKalpha1 and alpha2 activities in adipocytes from rats trained for 6 weeks. In conclusion, both acute and chronic exercise are significant regulators of AMPK activity in rat adipocytes. Our findings suggest that adrenaline plays a critical role in exercise-stimulated AMPKalpha1 and alpha2 activities in adipocytes, and that AMPK can function in the regulation of lipolysis.     

Defect in signal transduction at the level of the plasma membrane accounts for inability of insulin to activate pyruvate dehydrogenase in white adipocytes of lactating rats.

1. The mechanism responsible for the failure of insulin to activate pyruvate dehydrogenase (PDH) in white adipose tissue in vivo during lactation was investigated. 2. Insulin failed to increase PDH in isolated adipocytes from lactating rats. 3. Insulin binding to plasma membranes from adipocytes was unchanged by lactation. 4. Incubation of plasma membranes plus permeabilized mitochondria from adipocytes in the presence of insulin resulted in activation of PDH when the plasma membranes were obtained from virgin rats, whereas no activation was observed when plasma membranes from lactating rats were used. 5. The results show that the failure of insulin to activate PDH in adipose tissue from lactating rats is due to a failure of the signal-transduction system in the plasma membrane at steps subsequent to insulin binding to the insulin receptor.     

Metabolic interactions of glucose, acetoacetate and adrenaline in rat submaxillary gland in vitro.

1. The metabolic interactions between glucose, acetoacetate and adrenaline were studied in submaxillary-gland slices. 2. Acetoacetate (2.5 mM) inhibited glucose removal by 22% and entry of glucose carbon into the tricarboxylic acid cycle by 54%. 3. Acetoacetate caused an increase in (glucose 6-phosphate) together with an increase in (citrate), a finding that suggests that the phosphofructokinase step might be inhibited by the elevated (citrate). Support for this suggestion was obtained in experiments in which fluoracetate was used to elevate (citrate). 4. A further site of action of acetoacetate at the pyruvate dehydrogenase step was suggested by an increase in the lactate+pyruvate pool, and the finding that pyruvate removal and (3-14C)pyruvate oxidation were inhibited by acetoacetate. 5. Adrenaline, a stimulator of secretion by this tissue, increased glucose removal by 25%. Adrenaline increased glucose removal to the same extent when acetoacetate was also present in the incubation medium. In both cases the increase was accompanied by a fall in (glucose 6-phosphate). 6. Adrenaline also overcame the inhibition of pyruvate removal caused by acetoacetate. 7. The tissue (ATP) decreased by about 50% on addition of adrenaline, and a similar fall was observed in vivo after adrenergic stimulation by isoproterenol. 8. Omission of Ca-2+ from the medium prevented the fall in (glucose 6-phosphate) and (ATP) caused by adrenaline, although adrenaline was still able to stimulate glucose removal. The inhibitory effect of acetoacetate on gluocse removal was reversed by adrenaline, but there was no stimulation above the control rates. Inhibition of pyruvate removal by acetoacetate was not overcome by adrenaline in the absence of Ca-2+. 9. Dibutyryl cyclic AMP had no effect on glucose removal or on (ATP). 10. Possible mechanisms by which adrenaline can bring about its metabolic effects are discussed.     

Effect of theβ-adrenoceptor agonist BRL 26830 on fatty acid synthesis and on the activities of pyruvate dehydrogenase and acetyl-CoA carboxylase in adipose tissues of the rat

BRL 26830 is a thermogenic-adrenoceptor agonist which stimulates lipolysis and fatty acid oxidationin vivo. It also stimulates insulin secretion, and hence promotes glucose utilisationin vivo. The effect of this agent on white and brown adipose tissue of the rat was investigated. BRL 26830 increased the rate of fatty acid synthesisin vivo in white adipose tissue by 135% but reduced the rate of fatty acid synthesisin vivo in brown adipose tissue by 78%. The increase was abolished in white adipose tissue of streptozotocin-diabetic rats, indicating that the effect involved a rise in circulating insulin levels. The reduction in fatty acid synthesis in brown adipose tissues was associated with a reduction in the activity of acetyl-CoA carboxylase in the tissue consistent with a direct-adrenoceptor-mediated effect. BRL 26830 also increased the proportion of pyruvate dehydrogenase in its active formin vivo in brown adipose tissue and this increase was abolished in streptozotocin-diabetic rats. These findings illustrate different sensitivities of white and brown adipose tissues to combined-adrenergic and insulin stimulation.     

Stimulation of anaerobic metabolism in rats at high altitude hypoxia--adrenergic effects dependent on dietary states

1. Plasma lactate and pyruvate were increased more markedly in fed rats than in fasted rats exposed to an 8000 m altitude. 2. The increase in plasma lactate and pyruvate was enhanced and inhibited by the alpha 1-adrenergic antagonist prazosin and the beta-blocker propranolol, respectively, in fasted rats exposed to an 8000 m altitude. Blood glucose was not changed by adrenergic blockades under the same conditions. 3. Prazosin and propranolol showed no effect on glycolytic metabolites in plasma in fed rats submitted to an 8000 m altitude. Blood glucose of fed rats was increased by alpha 1-blockade during severe hypoxia. 4. In fasted rats whose energy metabolism depends on oxidation mainly, alpha 1- and beta-adrenergic receptors can participate in the stimulation of respiration and the glycogen degradation, respectively, during an exposure to severe hypoxia. In fed rats energy metabolism depends on glycolysis, which utilizes blood glucose as the substrate preferentially during hypoxia.     

Differential response of rat brown and white adipose tissue to environmental or nutritional stress.

1. In vivo fatty acid synthesis by brown adipose tissue was enhanced in rats exposed to cold (5 degrees C) or altitude (4300 m) for 7 days but was unaltered in rats exposed to heat (35 degrees C) for an equivalent period. In vivo fatty acid synthesis by white adipose tissue was depressed by cold exposure while altitude and heat exposure had no effect. 2. In vitro, CO2 production and lipid synthesis were elevated in brown adipose tissue from rats fasted for 4 days. Refeeding (4 days) such rats reversed these effects, leading to depressed values relative to those of control rats. In contrast, these metabolic events in white adipose tissue were decreased by fasting and increased compared to controls during subsequent refeeding.     

Does lead exposure influence liver protein synthesis in rats?

Glycogenolysis was stimulated by catecholamines in in vitro cultures of hepatic tissue of Xenopus laevis. Dose response curves showed that adrenaline and isoprenaline were equally effective while noradrenaline and phenylephrine were progressively less effective in eliciting glycogen breakdown. Neither oxymetazoline nor methoxamine had any effect on glycogenolysis. Administration of adrenaline to cultures was followed within 1 min by a rise in tissue cyclic AMP concentration and within 2 min by an increase in phosphorylase a activity. Both these responses were blocked by propranolol but little affected by phenoxybenzamine. These findings suggest that catecholamines activate glycogenolysis via a beta-adrenergic receptor in X. laevis and that alpha-adrenergic receptors play no role in regulating hepatic glycogenolysis in this species.     

Stimulation of flux through hepatic pyruvate dehydrogenase by 3-mercaptopicolinate

Isolated hepatocytes from 24-h-starved rats were used to assess the possible effect of Ahe hypoglycaemic agent 3-mercaptopicolinate on flux through the hepatic pyruvate dehydrogenase complex. Increasing the extraceIIular pyruvate concentration from 1 mM to 2 mM or 5 mM resulted in an increase in flux through pyruvate dehydrogenase and the tricarboxylic acid cycle as measured by¹⁴CO₂ evolution from [1-¹⁴C]pyruvate and [3-¹⁴C]pyruvate. Gluconeogenesis was inhibited by 3-mercaptopicolinate from both 1 mM and 2 mM pyruvate, but significant increases in malate and citrate concentrations only occurred in cells incubated with 1 mM pyruvate. Flux through pyruvate dehydrogenase was stimulated by 3-mercaptopicolinate with 1 mM pyruvate but was unaltered with 2 mM pyruvate. Dichloroacetate stimulated flux through pyruvate dehydrogenase with no effect on gluconeogenesis in the presence of I mM pyruvate. There was no effect of 3-mercaptopicolinate, administered in vivo, to 24-h-starved rats on the activity of pyruvate dehydrogenase in freeze-clamped heart or liver tissue, although the drug did decrease blood glucose concentration and increase the blood concentrations of lactate and alanine. Dichloroacetate, administered in vivo to 24-h-starved rats, increased the activity of pyruvate dehydrogenase in freeze-clamped heart and liver, and caused decreases in the blood concentrations of glucose, lactate , and alanine. The results suggest that 3-mercaptopicolinate increases flux through hepatocyte pyruvate dehydrogenase by an indirect mechanism.     

Tissue-specific modulation of insulin receptor mRNA levels in adrenaline-treated rats

Insulin receptor (IR) gene expression at the mRNA level was investigated in liver, hindlimb skeletal muscle, and epididymal adipose tissue of rats exposed to prolonged in vivo administration of adrenaline in relation to control rats. In the liver of adrenaline-treated rats, there were no differences in relation to controls when DNA and protein content were measured. In skeletal muscle, only a slight decrease in protein concentration was detected. By contrast, a clear increase in both protein and DNA content was observed in the adipose tissue of treated animals. Northern blot assays revealed two IR mRNA species of approximately 9.5 and 7.5 Kb in the three tissues from controls. Adrenaline treatment induced an increase of approximately 60% in the levels of both RNAs in adipose tissue but not in liver or skeletal muscle. These results provide evidence for an in vivo tissue-specific regulation of IR gene expression at the mRNA level in rats under an experimental condition of excess of catecholamines.     

Measurement of concentrations of metabolites in adipose tissue and effects of insulin, alloxan-diabetes and adrenaline

1. Methods are described for the extraction and assay of ATP, ADP, AMP, glucose 6-phosphate, l-glycerol 3-phosphate and citrate in rat epididymal adipose tissue incubated in vitro for 1hr. At this time of incubation rates of glucose uptake and outputs of glycerol, free fatty acids, lactate and pyruvate were shown to be constant. 2. In fat pads incubated in medium containing glucose (3mg./ml.) and albumin (20mg./ml.) the concentrations (in mmumoles/g. wet wt.) were: ATP, 70; ADP, 36; AMP, 9.0; glucose 6-phosphate, 3.0; l-glycerol 3-phosphate, 3.3; citrate, 8.1. 3. The volume of intracellular water calculated from ([(3)H]water space-[(14)C]sorbitol space), ([(14)C]urea space-inulin space) and (weight loss on drying-[(14)C]sorbitol space) was 1.4ml./100g. wet wt. of tissue. The intracellular volume was not changed by insulin, alloxan-diabetes or adrenaline. 4. When compared in terms of mumoles/ml. of intracellular water the concentration of ATP in adipose tissue was less than in heart and diaphragm muscles. The concentrations of ADP and AMP were greater both in absolute terms and relative to ATP. Insulin, alloxan-diabetes and adrenaline had no significant effects on the concentrations of the adenine nucleotides in adipose tissue. 5. The concentration of glucose 6-phosphate was increased by insulin and lowered by alloxan-diabetes and adrenaline. The concentration of l-glycerol 3-phosphate was increased by insulin, unchanged by alloxan-diabetes and lowered by adrenaline. The concentration of citrate was increased by adrenaline and alloxan-diabetes and unchanged by insulin. 6. The effect of glucose concentration in the medium on rates of glucose uptake in adipose tissue from normal rats and alloxan-diabetic rats was investigated. The K(u) of glucose uptake was 29-44mg./100ml. and the V(max.) was 0.77mg./g. wet wt. of tissue/hr. Insulin increased the V(max.) and alloxan-diabetes diminished it, but neither agent significantly altered the K(u). 7. The significance of these results in relation to control of metabolism of adipose tissue is discussed.     

Pathway of carbon flow during fatty acid synthesis from lactate and pyruvate in rat adipose tissue

The metabolism of pyruvate and lactate by rat adipose tissue was studied. Pyruvate and lactate conversion to fatty acids is strongly concentration-dependent. Lactate can be used to an appreciable extent only by adipose tissue from fasted-refed rats. A number of compounds, including glucose, pyruvate, aspartate, propionate, and butyrate, stimulated lactate conversion to fatty acids. Based on studies of incorporation of lactate-2-(3)H and lactate-2-(14)C into fatty acids it was suggested that the transhydrogenation sequence of the "citrate-malate cycle"(1) was not providing all of the NADPH required for fatty acid synthesis from lactate. An alternative pathway for NADPH formation involving the conversion of isocitrate to alpha-ketoglutarate via cytosolic isocitrate dehydrogenase was proposed. Indirect support for this proposal was provided by the rapid labeling of glutamate from lactate-2-(14)C by adipose tissue incubated in vitro, as well as the demonstration that glutamate can be readily metabolized by adipose tissue via reactions localized largely in the cytosol. Furthermore, isolated adipose tissue mitochondria convert alpha-ketoglutarate to malate, or in the presence of added pyruvate, to citrate. Glutamate itself can not be metabolized by these mitochondria, a finding in keeping with the demonstration of negligible levels of NAD-glutamate dehydrogenase activity in adipose tissue mitochondria. Pyruvate stimulated alpha-ketoglutarate and malate conversion to citrate and reduced their oxidation to CO(2). It is proposed that under conditions of excess generation of NADH malate may act as a shuttle carrying reducing equivalents across the mitochondrial membrane. Malate at low concentrations increased pyruvate conversion $$Word$$ citrate and markedly decreased the formation of CO(2) by isolated adipose tissue mitochondria. Malate also stimulated citrate and isocitrate metabolism by these mitochondria, an effect that could be blocked by 2-n-butylmalonate. This potentially important role of malate in the regulation of carbon flow during lipogenesis is underlined by the observation that 2-n-butylmalonate inhibited fatty acid synthesis from pyruvate, but not from glucose and acetate, and decreased the stimulatory effect of pyruvate on acetate conversion to fatty acids.     

Adaptive changes in enzyme activity and metabolic pathways in adipose tissue from meal-fed rats

A number of metabolic factors and the activity of a number of enzymes were determined in meal-fed (animals fed a single daily 2 hr meal) and nibbling (ad libitum-fed) rats. The dependency of the observed adaptive changes on the ingestion of carbohydrate was studied by feeding diets high in carbohydrate or fat. Glucose-6-phosphate dehydrogenase and NADP-malic dehydrogenase were more active in adipose tissue from high carbohydrate meal-fed rats than in tissue from ad libitum-fed rats. The activity in adipose tissue of isocitric dehydrogenase, 6-phosphogluconate dehydrogenase, and NAD-malic dehydrogenase did not increase significantly in response to meal-feeding the high carbohydrate diet. No increase in lipogenesis or enzyme activity could be demonstrated in adipose tissue from rats meal-fed a high fat diet. Lipase activity of adipose tissue was increased by high carbohydrate meal-feeding and decreased by feeding a high fat diet. The in vitro uptake of palmitate-1-(14)C by adipose tissue was depressed by a high fat diet and enhanced in rats meal-fed a high carbohydrate diet. Diaphragm or slices of liver from high fat-fed rats oxidized palmitate-1-(14)C more rapidly than did tissue from ad libitum-fed animals. Evidence is presented for the quantitative importance of citrate as a source of extramitochondrial acetyl CoA in adipose tissue of meal-eating and ad libitum-fed rats. The relationship of extramitochondrially formed citrate to the NAD-malic dehydrogenase-malic enzyme system in adipose tissue is discussed.     

Clenbuterol stimulated increase of plasma free fatty acids in reserpinized pigs

1. Previous studies indicate the beta-adrenergic agonist, clenbuterol, does not stimulate porcine adipose tissue lipolysis or cAMP concentration in vitro but increases plasma free fatty acid concentrations when infused, implying an indirect mechanism in vivo. 2. One indirect mechanism is the release of endogenous catecholamines to increase adipose tissue lipolysis and raise plasma free fatty acids. 3. In pigs treated with reserpine to deplete endogenous catecholamines, clenbuterol infusion increased plasma free fatty acids concentration suggesting that this increase in vivo did not result from release of endogenous catecholamines.     

Effects of carbohydrate availability on lipogenesis in sheep

1. Lipogenesis in sheep liver and adipose tissue was investigated by incorporation studies in vitro with radioactive glucose and acetate and by assays of key enzymes. 2. Carbohydrate availability to sheep was increased by feeding on a diet containing 70% soluble carbohydrate, by infusing glucose into the abomasum or by direct intravenous infusion of glucose. 3. Under these conditions lipogenesis from glucose and acetate was increased from very low values in lìver and adipose tissue, especially in those animals where rumen fermentation was by-passed by glucose infusion. 4. Large increases in the activities of ATP citrate lyase (EC 4.1.3.8) and NADP-malate dehydrogenase (EC 1.1.1.40) occurred in both tissues when lipogenesis was increased. 5. No adaptations were found in the activities of pyruvate carboxylase (EC 6.4.1.1) in adipose tissue, glucokinase (EC 2.7.1.2) in liver or 3-hydroxybutyrate dehydrogenase (EC 1.1.1.30) in liver. It is proposed that the absence of these enzymes is not related to glucose availability. 6. The effect of glucose on liver lipogenesis was to increase conversion of acetate into lipid. 7. This effect also occurred in adipose tissue, but in this tissue glucose also became a quantitatively important precursor of triglyceride fatty acid.