Free Fatty Acid Mobilization Research Articles

Determination of splanchnic secretion rate of plasma triglycerides and of total and splanchnic turnover of plasma free fatty acids in man.

Abstract. A method has been developed whereby the splanchnic secretion rate of plasma triglycerides (TG) and the splanchnic uptake and mobilization of plasma free fatty acids (FFA) can be measured in man. The method includes constant intravenous infusion of albumin‐bound 3H‐labelled palmitate, and simultaneous sampling of blood from the hepatic vein and an artery.The methodological problems associated with the quantitative determination of the small hepatio venous‐arterial differences of labelled and unlabelled plasma TG and FFA have been studied. By performing ten estimates on each hepatic vein and arterial sample, analytical precision was increased sufficiently to detect significant hepatic venous‐arterial differences in TG concentration and radioactivity.The splanchnic secretion rates of labelled plasma TG were found to be constant 3 hours after beginning the continous infusion of the precursor 3H‐palmitate. The plasma TG turnover was calculated according to three different methods: the chemical, the isotope and the plasma TG clearance methods. The mean values and standard deviations of the three methods were 59 ± 105, 29 ± 12 and 37 ± 22 μmoles/min.The splanchnic uptake of plasma FFA was estimated to be between 225 and 269 μmoles/min and the splanchnic mobilization of plasma FFA was between 76 and 120 μmoles/min.

Regulation of ketogenesis and clinical aspects of the ketotic state

Recent studies of the regulation of ketogenesis are reviewed. Under circumstances of relative or absolute insulin deficiency there is a mobilization of free fatty acids from adipose tissue to the liver. While an increased delivery of fatty acids to this organ is important in providing substrate for ketone body formation, it is emphasized that enhanced uptake of fatty acids by the liver is not sufficient in itself to initiate maximal ketogenesis. It appears likely that a major determinant of the rate of ketogenesis is competition for the fatty acid substrate between the β-oxidative and triglyceride synthesizing pathways. While it is widely held that the rate of triglyceride synthesis is primary and that only those fatty acids not utilized for esterification become available for oxidation, evidence for the reverse sequence is presented. It is considered likely that fatty acids are utilized for triglyceride synthesis only insofar as they escape uptake and oxidation in the mitochondria. Regardless of the mechanism, fatty acid oxidation is increased in the ketotic state with the consequence that acetyl-CoA production is accelerated. Since the utilization of acetyl-CoA for fatty acid synthesis and, to a much lesser extent, its oxidation in the Krebs cycle is impaired, the synthesis of acetoacetate and β-hydroxybutyrate is stimulated to a remarkable degree. The hepatic overproduction of ketones appears to be coupled to a limited capacity for their utilization by peripheral tissues, the combined effect of which accounts for the life-threatening acidosis seen in diabetic coma. From a clinical standpoint, newer studies relating to the treatment of diabetic ketoacidosis have been covered, with particular attention paid to the problems of late cerebral edema, paradoxical acidification of the cerebrospinal fluid during treatment, shifts of the oxygen dissociation curve due to 2,3-diphosphoglycerate depletion and initial hypokalemia. Recommendations for therapy designed to minmize complications are presented.

Inhibition by β-hydroxybutyrate of lipolysis induced by sympathetic nerve activity in canine subcutaneous adipose tissue in situ

d,l-β-hydroxybutyrate was infused in the arterial blood stream supplying the isolated canine subcutaneous adipose tissue at a rate producing a concentration of the d (−) form of 2–5 m M. The vascular effects were small and inconsistent. Glucose uptake increased, and the basal free fatty acid (FFA) release decreased despite and unchanged mobilization of glycerol. The rate of lactate release was somewhat reduced. The mobilization of glycerol induced by nerve stimulation was inhibited by approximately 50%, and the FFA mobilization by 70%. On the other hand, there was no antagonism of the vasoconstrictor effect of nerve stimulation. About 90% of the d (−) β-hydroxybutyrate administered was extracted in a single passage. The results indicate that β-hydroxybutyrate in concentrations comparable to those that might occur during prolonged fasting inhibits activation of lipolysis by nerve stimulation, but has little effect on basal lipolysis.

Biochemical studies on the mechanism of action of liver poisons II. Induction of fatty livers

Administration of adenine or its nucleotide derivatives (3′(2′)-AMP, 5′-AMP and ATP) to rats prevented the induction of fatty livers by ethionine, carbon tetrachloride and Pactamycin, but failed to relieve the inhibition of protein synthesis in vivo and the derangement of the triglyceride transport from the liver caused by these hepatotoxins. The antidotal effect of the exogenous ATP precursors against the steatogenic action of the liver poisons appeared to be unrelated to the reversal of the ATP depletion observed in ethionine poisoning, since no appreciable changes in the hepatic ATP content occurred in rats treated with carbon tetrachloride or Pactamycin under the conditions employed in this study. Adenine and its congeners induced a marked depression of the plasma free fatty acid level and a concomitant elevation of the blood glucose concentration. Adrenalectomy abolished the hyperglycemic effect of adenine nucleotides but allowed their depressive influence on the plasma free fatty acids to persist, indicating that the latter phenomenon was not entirely attributable to the well-known inhibitory effect of glucose on free fatty acid mobilization. It was concluded that adenine and the congerous nucleotides exerted their protective action against fatty liver induction by curtailing the influx of free fatty acids into the liver and thereby limiting the extent of triglyceride synthesis. This interpretation is also supported by the correlation between the female-sex dependency of the ethionine-induced hypoglycemia and increased fatty acid mobilization on the one hand, and the greater susceptibility of the female rat to the steatogenic action of this poison on the other.

Some effects of bromotrifluoromethane inhalation on myocardial glycolysis

Bromotrifluoromethane (CBrF 3) would have considerable potential as a closed environment fire extinguishing agent, except for its membership in that large group of hydrocarbons capable of precipitating irregular heart action when inhaled by persons with elevated levels of blood epinephrine. These experiments were an effort to determine whether myocardial glycolysis was impaired in male Wistar rats breathing 79 21 CBrF 3 O 2 and challenged with 1-epinephrine in what would ordinarily constitute subtoxic doses. CNS effects were the major observations in rats exposed to both CBrF 3 and epinephrine; 17 of the 20 rats so exposed suffered respiratory arrest within 40 min, and several of them exhibited erratic, convulsive behavior prior to exhibiting respiratory difficulties. All control rats survived, and myocardial levels of glycolytic intermediates were compared in animals breathing air or CBrF 3 O 2 , with and without epinephrine challenge, using “crossover plots.” With air-epinephrine and CBrF 3-epinephrine there were crossovers (activation) at phosphofructokinase, and the general picture was consistent with the CBrF 3 induction of respiratory depression and hypoxia, resulting in the mobilization and intracellular accumulation of free fatty acids.

Factor in colostrum causing mobilization of free fatty acid in newborn calves.

SummaryFeeding colostrum or fat‐free colostral whey to newborn, previously unbuckled calves was followed by a four‐fold increase in free fatty acid concentration in thoracic duct lymph and blood plasma. There was no increase in free fatty acid concentration when newborn calves were fed milk. The fatty acid composition of lymph free fatty acid in calves fed colostrum more closely resembled per renal fat than lipid of dietary origin. It was apparent that colostrum contains a factor responsible for the mobilization of depot fat in newborn calves.In a previous paper from this laboratory attention was drawn to a pronounced increase in free fatty acid concentration in thoracic duct lymph after feeding colostrum to newborn unsuckled calves (Shannon and Lascelles, 1969). This increase occurred before a significant concentration of chylomicrons appeared in the lymph, suggesting that it was not associated with absorption of dietary lipid. A possible interpretation of these results is that colostrum contains a factor responsible for the mobilization of free fatty acid from the fat depots of the newborn calf. The opportunity to test this hypothesis arose in experiments primarily designed to compare the pattern and efficiency of lipid absorption by way of the lymphatic system in newborn calves fed colostrum or milk (Gooden, Brandon, Hartmann and Lascelles, 1971).

Heparin-induced release of lipase activity from perfused canine subcutaneous adipose tissue.

SummaryThe effects of heparin, histamine, and Compound 48/80 on the release of free fatty acids (FFA), glycerol, and venous plasma lipolytic activity (VPLA) from the isolated perfused canine subcutaneous adipose tissue in situ was studied. Intra-arterial administration of heparin with dosages between 5 to 500 μg produced an increase in VPLA release which was dose dependent. The VPLA release was decreased after repeated injection of heparin. Heparin administration did not alter the release of FFA and glycerol. Histamine and Compound 48/80 increased FFA and glycerol release, but produced no effect on VPLA release. The results do not support the contention concerning a possible role of mast cell heparin in the regulation of lipid metabolism in canine subcutaneous adipose tissue but confirm the previous findings that mast cell histamine may exert some effect in the mobilization of FFA.

Effect of Insulin Injections Upon Plasma Free Fatty Acids (F.F.A.) and Lipolysis of Adipose Tissues of White Leghorn Hens

INSULIN, parenterally administered into mammalian species leads to a fall of plasma free fatty acids (F.F.A.) (Engel, 1962; Vaughan and Korn, 1962). In contrast, administration of insulin into domestic fowl leads to an increase in plasma F.F.A. (Heald et al., 1965; Lepkovsky et al., 1967). Heald et al. (1965) suggested that the action of insulin was due to a glucagons impurity since adipose tissue of the fowl is very responsive to treatment with glucagon (Grande, 1970; Heald et al., 1965). That the increase in plasma F.F.A. in response to administration of insulin was due to insulin was shown by Lepkovsky et al. (1967) who used glucagon-free insulin. While increases in plasma F.F.A. have been used as an index of mobilization of free fatty acids from the adipose tissues, (Gibson and Nalbandov, 1966), it is possible for plasma F.F.A. to originate elsewhere such as in the triglycerides of the blood. If…

Efflux of free fatty acids from adipose tissue

ARTICLESEfflux of free fatty acids from adipose tissueRJ Schimmel, and HM GoodmanRJ Schimmel, and HM GoodmanPublished Online:01 Jul 1971https://doi.org/10.1152/ajplegacy.1971.221.1.118MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByHistorical perspectives in fat cell biology: the fat cell as a model for the investigation of hormonal and metabolic pathwaysMax Lafontan15 January 2012 | American Journal of Physiology-Cell Physiology, Vol. 302, No. 2F ATTY A CID T RANSPORT A CROSS M EMBRANES : Relevance to Nutrition and Metabolic PathologyAnnual Review of Nutrition, Vol. 22, No. 1Muscle contractile activity increases fatty acid metabolism and transport and FAT/CD36Arend Bonen, David. J. Dyck, Azeddine Ibrahimi, and Nada A. Abumrad1 April 1999 | American Journal of Physiology-Endocrinology and Metabolism, Vol. 276, No. 4Membrane transport of long-chain fatty acids: evidence for a facilitated processJournal of Lipid Research, Vol. 39, No. 12Glucose-stimulated lipolysis in rainbow trout, Oncorhynchus mykiss, liverFish Physiology and Biochemistry, Vol. 10, No. 3The reversible inhibition by carbonyl cyanide m-chlorophenyl hydrazone of epinephrine-stimulated lipolysis in perifused isolated fat cellsBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, Vol. 666, No. 3Characterization of lipolytic responses of isolated white adipocytes from hamstersBiochimica et Biophysica Acta (BBA) - General Subjects, Vol. 496, No. 2Regulation of lipid metabolism in the normal pig aorta Part 1. Influence of insulin and epinephrine on lipid synthesis from [U14C] glucoseAtherosclerosis, Vol. 23, No. 2Inhibition of free fatty acid mobilization by colchicineJournal of Lipid Research, Vol. 15, No. 3Displacement into incubation medium by albumin of highly unsaturated retina free fatty acids arising from membrane lipids19 October 2001 | FEBS Letters, Vol. 40, No. 1Response of isolated white fat cells to anti-malarial drugsBiochemical Pharmacology, Vol. 22, No. 23Cell-associated nonesterified fatty acid levels and their alteration during lipolysis in the isolated mouse adipose cellJournal of Lipid Research, Vol. 14, No. 6 More from this issue > Volume 221Issue 1July 1971Pages 118-122 Copyright & PermissionsCopyright © 1971 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1971.221.1.118PubMed5555776History Published online 1 July 1971 Published in print 1 July 1971 Metrics

Effect of a combination of propranolol and nicotinic acid on the inhibition of norepinephrine-induced elevations of serum triglyceride, serum glycerol, and plasma free fatty acids in the dog

A study was made of methods to reduce the concentration of serum triglyceride by suppressing plasma free fatty acid mobilization through a dual modification of their release mechanism. Serum triglyceride, serum glycerol, serum cholesterol and plasma free fatty acids were measured under the influence of infusions of norepinephrine and low doses of propranolol and nicotinic acid in dogs. During a 4 hr infusion of norepinephrine, serum triglyceride rose 20 per cent. The addition of individual infusions of low doses of propranolol and nicotinic acid had a small effect. However, the infusion of low doses of these two agents in combination had an additive effect, causing serum triglyceride to fall 25 per cent. A similar inhibitory effect of propranolol and nicotinic acid used in combination was noted in a sustained reversal of norepinephrine-induced elevations of serum glycerol and plasma free fatty acids. Serum cholesterol was not changed over the 4-hour period by any agent as compared to saline. The effects of small doses of propranolol and nicotinic acid used in combination on the inhibition of norepinephrine-induced elevations of serum triglyceride may be explained by their additive inhibition of plasma free fatty acid mobilization.

Effect of free fatty acid mobilization on the electrophoretic mobility of α-lipoproteins in the dog

Dogs were given infusions of norepinephrine and subsequent additional infusions of propranolol and nicotinic acid over a 4-hr period. Under different physiological conditions, α-lipoproteins of three different electrophoretic mobilities were identified by means of paper electrophoresis; they were designated α-lipoproteins X, Y, and Z. During norepinephrine infusion, α-lipoprotein Y fell from 45% (of all lipoproteins) to 14%. There was a reciprocal rise in α-lipoprotein Z. On the other hand, α-lipoprotein X was not significantly changed. There was evidence that α-lipoprotein Y was progressively transformed into α-lipoprotein Z by increasing plasma FFA concentrations. The percentages of both α-lipoproteins Y and Z returned to original values after the dogs were given either nicotinic acid or propranolol. The alterations in the α-lipoprotein peaks Y and Z were rapid, being noted within 5 min of change in plasma FFA concentration. However, there appeared to be a threshold of plasma FFA concentration of 1200 μEq/liter, below which no changes in α-lipoproteins were noted. It was concluded that α-lipoprotein Y is rapidly, progressively, but reversibly transformed into α-lipoprotein Z by binding to plasma FFA above a threshold level of 1200 μEq/liter. However, α-lipoprotein X does not appear to be involved in the binding of plasma FFA.

Synergistic effect of propranolol and nicotinic acid on the inhibition of plasma free fatty acid release in the dog.

Fatty acid mobilization was effected in 24 anesthetized dogs by infusion of norepinephrine over a four-hour period. Infusions of propranolol and nicotinic acid at various doses, individually and in combination, were added and free fatty acid levels were serially determined. Synergistic action of the two agents was apparent in that minimally effective concentrations of the two agents when used in combination suppressed the release of free fatty acids to 29 percent of levels achieved with norepinephrine (1,186 µEq/L). and 70 percent of levels in saline control animals (501 µEq/L). Large individual doses were no more effective than low doses used in combination. The synergistic action of propranolol and nicotinic acid in the suppression of free fatty acid mobilization may be explained by the action of these two agents on the inhibition of the adenyl cyclase system of the adipose tissue cell. This synergistic action in reducing plasma free fatty acids and their effect on lipid synthesis would allow the use of smaller doses that could reduce the risk of side effects.

Lipid metabolism during heavy and moderate exercise

The purpose of this investigation was to determine the effects of moderate and heavy exercise on free fatty acid (FFA) mobilization and utilization in human subjects. Thirty-five male subjects performed two exercise tests on a motor driven treadmill. Fifteen minutes of moderate work (40 to 50% maxVO2) was followed by an additional 15 minutes of moderate work in one test, and by 15 minutes of heavy work (80 to 90% maxVO2) in the second test. Plasma glycerol concentration increased during both heavy and moderate exercise. Plasma FFA concentration decreased during the first 15 minutes of moderate exercise; when moderate exercise was continued for 15 more minutes, plasma FFA concentration rose toward the former resting level. When heavy exercise was performed, following 15 minutes of moderate exercise, the initial decline in plasma FFA concentration continued. During heavy exercise the percentage in plasma FFA of C18:2 decreased, while that of C18:2 increased. The opposite was true during moderate exercise. It is concluded that FFA mobilization and utilization were enhanced during both moderate and heavy exercise. FFA utilization during heavy exercise exceeded that during moderate exercise. Blood lactate concentration increased only when heavy exercise was performed and did not appear to inhibit FFA mobilization.

Studies on aminoacetonitrile and its related compounds. IV. Effect of aminoacetonitrile on experimental fatty liver

Effect of aminoacetonitrile on hepatic injuries by treatment of rats with carbon tetrachloride was tested. The possible participation of the sympathetic nervous system in the development of fatty liver was also examined. A long-lasting elevation of free fatty acids was observed in plasma of rats after an administration of CCl4. The increase of plasma fatty acids and liver lipid by CCl4 was partially prevented by dibenzyline, propranolol, and trimethidium. The fatty liver produced by CCl4 was markedly potentiated by phenelzine but not by pyrogallol. When 50 to 100 mg/kg of aminoacetonitrile was injected before poisoning with CCl4, the liver dysfunction was clearly prevented. The lipid accumulation in the liver produced by CCl4 was partially prevented by the administration of 50 mg/kg of aminoacetonitrile, which also inhibited the elevation of plasma fatty acids induced by the administrations of CCl4 and morphine or by exposing the rats to cold, but not that induced by norepinephrine, etc. The protective effect of aminoacetonitrile on the mobilization of free fatty acids and lipid accumulation procuced by CCl4 was not observed in reserpinized rats. It is concluded from these results that CCl4 increases the mobilization of free fatty acids by stimulating the sympathetic nervous system. Furthermore, it is considered that the effect of aminoacetonitrile on the lipid accumulation induced by CCl4 is due to inhibition of the mobilization of fatty acids.

Pharmacological control of lipid transport.

The hormonal and nervous mechanisms involved in free fatty acid mobilization from adipose tissue in different mammalian species are described and the pharmacological control of these mechanisms underlined. The mode of action of antiadrenergic agents, nicotinic acid derivatives and adenosin derivatives are described in detail. The practical application of the inhibition of free fatty acid mobilization for the control of plasma and tissue triglyceride levels are outlined.

Free fatty acids during acute myocardial infarction

Free fatty acids (FFA) are elevated in plasma soon after the onset of symptoms associated with developing myocardial infarction. Levels above 1200 mu Eq./L. are associated with a significantly increased incidence of serious ventricular arrhythmias, heart block and sudden death. Evidence is presented from experimental myocardial infarction in dogs to show that high levels of FFA can themselves cause arrhythmia, although catecholamines are mainly responsible for the mobilization of FFA during clinical episodes of acute myocardial ischemia. It is postulated that high concentrations of FFA irrespective of the mode of elevation have a deleterious effect on the function of the heart during hypoxia. These observations offer a new therapeutic approach to the management of arrhythmias and of acute myocardial infarction. Attention should be directed to blocking FFA release from adipose tissue and to providing the hypoxic myocardial cells with a concentration of glucose which will provide adequate substrate for all energy requirements of the heart.

Effects of ethanol on free coenzyme A, free carnitine and their fatty acid esters in rat liver

1. 1. Ethanol increases liver triglycerides. In order to elucidate the mechanism of this fat deposit, the effect of ethanol on CoA, carnitine and their fatty acid esters in the liver was investigated. 2. 2. A single dose of ethanol (5 g/kg) increases CoA concentration in the liver of rats kept on a standard diet. 2 h following the administration of ethanol, the ratio long-chain acyl-CoA/free CoA remains nearly unchanged as compared to control animals. After 12 h, when liver triglycerides are markedly elevated, this ratio shifts distinctly in favor of the long-chain acyl-CoA. 3. 3. In protein-deficient rats, the long-chain acyl-CoA content in the liver increases markedly as compared to controls given a standard diet, while the level of free CoA drops. Under these conditions, acute ethanol application results in extremely high long-chain acyl-CoA levels. 4. 4. After ethanol administration, carnitine concentration alters in a similar way to CoA concentration. However, after ethanol administration, the increase of longchain acyl-carnitine is much less pronounced than the increase of acyl-CoA. Thus, the ratio long-chain acyl-carnitine/free carnitine shows minor alterations during ethanol oxidation. 5. 5. From these results, it is suggested that under conditions in which ethanolinduced lipid accumulation in the liver is observed, fatty acid synthesis is reduced by a negative feedback inhibition of the acetyl-CoA carboxylase reaction by high levels of long-chain acyl-CoA. These findings support the assumption that fat infiltration in the liver after acute ethanol administration is mainly caused by enhanced mobilization of free fatty acids from adipose tissue and not by stimulation of fatty acid synthesis in the liver.

The metabolism of glucose, acetate, palmitate, stearate and oleate in pigs

1. Isotope dilution techniques were used to measure the rates of entry and oxidation of glucose, acetate, palmitate, stearate and oleate in fed and fasted (16 h) pigs.2. Glucose entry rates measured in eight fed and five fasted (16 h) pigs were 20.6 and 8.0 mg/min per kg0.75(mean values) respectively. The entry rates in fed pigs were lower than the calculated rates of glucose uptake from the alimentary tract, and the validity of glucose entry rates determined under these conditions is discussed.3. Acetate entry rates were unrelated to the fibre content of the diet, and acetate produced from endogenous metabolism was the main contributor to total acetate production.4. Increased rates of entry and oxidation of palmitate, stearate and oleate were observed in fasted pigs.5. Glucose production in fasted pigs was inhibited by raising the concentration of blood glucose. Infusion of insulin in the fed pig caused a decrease in glucose production and a simultaneous reduction in the mobilization of free fatty acids. When blood glucose concentrations fell below about 55 mg/100 ml the release of free fatty acid into the circulation was restored.

Inhibited Lipolysis by Hypoxia: Its Potential Role in Neonatal Thermogenesis

Because of impaired thermogenesis, cold stress is poorly tolerated by hypoxic neonates. Since free fatty acids (FFA) are a major fule for heat production, deficient FFA mobilization could contribute to reduced heat production at low oxygen tensions. In order to determine the effect of hypoxia upon cold-stimulated lipolysis and its potential role in thermogenesis, plasma glycerol and FFA levels, and deep rectal temperature were studied in cooled puppies made hypoxic. Upon lowering ambient temperature from 30 to 20°C, levels of plasma glycerol and FFA increased in 12 puppies ventilated with air (PaO2 < 75 mm Hg). In contrast to persisting high plasma glycerol and FFA levels with continued cooling in the control group, plasma glycerol fell from 172 ± 8% to 85 ± 10% and FFA from 206=25% to 105±13% mean control values (mean ± S.E.) in six animals made hypoxic (PaO2 25–35 mm Hg) for 45 min. Comparison of core temperatures during cooling revealed that the rate of temperature fall was accelerated by hypoxia, and that the mean peak fall was significantly greater in hypoxic than in control animals (p < 0.005). These observations indicate that lipolysis stimulated by cold stress is inhibited by hypoxia, which results in the reduction of FFA as a fuel source. This loss of FFA as a fuel may explain the handicap to thermogenesis observed in the hypoxic neonate.

The effect of chronic hypoxia on in vitro lipolysis in the rat.

The responsiveness of the lipolytic system in chronically hypoxic rats (14 500 ft) was assessed by the in vitro release of free fatty acids (FFA) and glycerol, measured aerobically and anaerobically, in epididymal fat pads from fed, fasted, and fasted–refed animals. Basal aerobic release of FFA for fed rats was significantly higher in the altitude (ALT) group. In fasted rats both basal and norepinephrine (NE)-stimulated release of FFA and glycerol was higher when compared with heavier sea level (SL) controls. However, weight-matched (younger) controls showed no difference in release rates. Anaerobic NE-stimulated release of FFA, glycerol, and lactate was higher in ALT rats than in weight-matched SL controls only in those animals fasted and refed a high carbohydrate diet. Fat pad glycogen content in such animals was 0.207 mg/100 mg tissue for SL and 0.384 for ALT. Anaerobic in vitro FFA mobilization in adipose tissue from fasted–refed ALT rats is more sensitive to NE, and this physiological advantage may be a reflection of a greater potential for glycogen storage in the fat tissue of these acclimated animals. Additionally, weight matching is necessary in evaluating altitude-stressed animals, and use of dietary restrictions to obtain controls of equal age and weight may yield misleading metabolic data.