Oxidation of palmitate by human skeletal muscles in vitro. Method and normal values.

The conditions of determination of the in vitro incorporation rate of palmitate-carbon into CO2 in human skeletal muscles were studied. Muscle biopsies were taken from 25 patients with nonmuscular diseases and incubated in a metabolic shaker with KRP as medium and palmitate as substrate. Substrate saturation was achieved beyond a palmitate concentration of 2.5 mmol/1, and the incorporation rate was linear with time for 2 hr. The activity of 3-hydroxy-acyl-CoA-dehydrogenase (ACDH), an enzyme involved in the beta-oxidation, was also determined. Both the incorporation rate of palmitate-carbon into CO2 and the activity of ACDH were higher in the leg muscles than in the abdominal muscles. Significant positive correlations were found between the incorporation rate of palmitate-carbon into CO2 and the ACDH activity, and between the incorporation rate and the phospholipid concentration in muscles. These correlations indicate that this in vitro system is valid for evaluation of the metabolism of fatty acids in skeletal muscle tissue.     

Metabolic Activity in Rat Skeletal Muscle:Effect of Intermittent Hypoxia

Abstract. In order to determine whether hypoxia is a trigger for changed metabolic activity in muscle tissue, rats were exposed to intermittent hypoxia of varying degree (5% 0₂, 8% 0₂, 10% 0₂, 12% 0₂, 15% 0₂ in N₂) 3 h per day for 1–4 weeks. The effects of hypoxia on the rate of incorporation of glucose-carbon into glycogen, lipids, carbon dioxide and lactate and on succinic oxidase activity in skeletal muscle tissue were determined. Rats intermittently exposed to 5% oxygen in nitrogen for one week showed a significant decrease of the rate of incorporation of glucose-carbon into lipids and carbon dioxide and a significant decrease in succinic oxidase activity. In rats exposed to 8 and 10% 0₂ a significant increase of the incorporation rate of glucose-carbon into glycogen, lipids and carbon dioxide was found after 1 and 4 weeks and succinic oxidase activity increased after 4 weeks. The phospholipid concentration in muscle tissue decreased after 8 and 10% 0₂ exposure for 4 weeks. In the rats exposed to 8% oxygen for 4 weeks the protein concentration of muscle tissue increased significantly.–Based on these results it is suggested that the change of the glycolytic activity and succinic oxidase activity in muscle tissue after physical training and in arterial insufficiency are induced by hypoxia in the muscles.     

Metabolic Activity in Human Skeletal Muscle Effect of Peripheral Arterial Insufficiency

Abstract Succinic oxidase activity and the incorporation rates of glucose-carbon into glycogen, lipids, lactate and carbon-dioxide were studied in vitro in samples of skeletal muscle taken from patients with peripheral arterial insufficiency.
In the patients with intermittent claudication significantly increased succinic oxidase activity and incorporation rates of glucose-carbon were found in muscle tissue taken from the medial head of the gastrocnemius muscle. In patients with evidence of ischaemia at rest the metabolic activity in the muscle tissue was similar to the controls but significantly lower than in the patients with claudication on all points.     

运动状态下脂肪氧化的调节

背景：传递到工作肌群血浆中的脂肪酸主要来自于储存在脂肪组织中的三酰甘油的分解。在大强度运动时,脂肪酸氧化不能支持能量的需要,可能是骨骼肌氧化脂肪酸能力受限。目的：综述运动时脂肪氧化调节机制方面的研究,提出目前脂肪氧化调节机制方面亟待解决的问题。方法：以＂exercise,fatty acid oxidation,intensity,carnitine,acetylcarnitine,mitochondria＂为检索词,检索PubMed数据库1995至2012年发表的相关文章,文献语种限制为英文。纳入与运动时脂肪氧化调节机制相关的内容,排除重复性研究。结果与结论：计算机初检得到94篇文献,排除无关重复的文献,保留56篇进行综述。运动时脂肪酸氧化存在多种可能调节的步骤,从脂肪组织脂肪分解到骨骼肌线粒体的代谢。目前,最有吸引力的脂肪酸氧化调节候选剂是肌肉代谢物肉碱。它是肉毒碱棕榈酰转移酶1调节和脂肪酸氧化的基本。大强度运动时,糖酵解迅速增加,为线粒体提供过多乙酰辅酶A,并被肉碱缓冲,生成乙酰肉碱。相应地,肌肉自由肉碱下降,降低肉毒碱棕榈酰转移酶1活性,从而降低运输脂肪酸进入线粒体的能力,也降低脂肪酸氧化率。因此,糖原迅速分解和糖酵解对抑制脂肪酸的氧化产生主要影响。     

Paradoxical Effects of Clofibrate on Liver and Muscle Metabolism in Rats: INDUCTION OF MYOTONIA AND ALTERATION OF FATTY ACID AND GLUCOSE OXIDATION

Chronic clofibrate intake, on occasion, results in a muscular syndrome in man. We have investigated the effects of chronic clofibrate administration in rats on the electrical activity of a skeletal muscle (gastrocnemius), its composition, and its oxidation of palmitate and glucose. These effects have been compared with those in the liver. Clofibrate administration altered electromyographic pattern of gastrocnemius muscle (characteristic of myotonia), decreased its protein content, and impaired its oxidation of palmitate and glucose. These effects were quite different in the liver, because clofibrate intake increased the liver protein content and oxidation of palmitate without affecting the oxidation of glucose by this tissue. Whereas chronic clofibrate administration markedly increased the concentration of carnitine as well as the activity of mitochondrial carnitine palmitoyl-transferase in the liver, it decreased the activity of this enzyme in the gastrocnemius muscle without a significant effect on carnitine concentration in this tissue. Greater in vivo fatty acid oxidation by clofibratefed than by control rats was evidenced (a) by greater rate of production of (14)CO(2) in the expired air after injection of a tracer dose of [(14)C]palmitate and (b) by greater plasma and tissue concentrations of ketone bodies. We conclude that (a) paradoxical effects of clofibrate on fatty acid oxidation by the liver and skeletal muscle are related to changes in the activity of carnitine acyltransferase, (b) an increase in hepatic fatty acid oxidation may contribute to hypolipidemic effect of clofibrate, and (c) impairment of fatty acid and glucose oxidation by the muscle may be a factor in the development of muscular syndrome in patients receiving clofibrate treatment.     

Metabolic Activity of Skeletal Muscle in Patients with Peripheral Arterial Insufficiency

Abstract. 18 patients with intermittent claudication were studied to find some explanation for the beneficial effect of physical training on their symptoms. The patients were randomly allocated to a training group and a placebo-treated control group. The effect of treatment on serum lipids, muscle lipids and glycogen, walking tolerance, calf blood flow, muscle succinic oxidase activity and the in vitro incorporation rate of glucose-carbon into various metabolites were studied.
In the control group none of these parameters were changed.
In the trained group the following significant changes were found: Walking tolerance improved; muscle contents of cholesterol and phospholipids increased, as did succinic oxidase activity and the incorporation rate of glucose-carbon into glycogen, lipids and carbon dioxide. Incorporation of glucose-carbon into lactate decreased.
The improvement in walking tolerance was correlated with the altered pattern of metabolic activity but was not associated with increased calf blood flow. It is concluded that metabolic changes in skeletal muscles may be important in explaining the beneficial effects of physical training in patients with peripheral arterial insufficiency.     

Protein synthesis in human skeletal muscle tissue: influence of insulin and amino acids

Abstract. The effects of a mild stimulation of endogenous insulin secretion on the rate of incorporation in vitro of amino acids into human skeletal muscle protein were compared with the effects on this rate of adding insulin and amino acids in vitro . An intravenous infusion of 0.83 mmol glucose per kg body weight increased both plasma glucose and insulin levels significantly. The rate of incorporation of leucine into protein in isolated muscle fibres was significantly higher if the subjects had received the glucose infusion. Both insulin and a high concentration of amino acids in the incubation medium stimulated this rate. Amino acids stimulated the rate more than insulin and insulin did not further stimulate the amino acid-stimulated rate. On the other hand, the stimulation of the rate of incorporation by amino acids was the same whether the subjects had received saline and were thus in a basal state or whether they had been infused with glucose (which itself stimulated the rate). The rate of incorporation of leucine was correlated with the tissue concentration of RNA but the correlation was weaker when the rate was stimulated by amino acids than under other experimental conditions. Leucine stimulated the rate of incorporation of phenylalanine but phenylalanine did not stimulate the rate of incorporation of leucine.
It is concluded that the rate of incorporation rate of amino acids into protein in isolated human skeletal muscle fibres is subjected to hormonal and amino acid control.     

Glucose tolerance in relation to skeletal muscle enzyme activities in cancer patients.

Glucose metabolism and skeletal muscle enzyme activities were studied in nineteen cancer patients and twelve matched controls. The fasting insulin values were normal but the fasting glucose values and the sum of glucose were increased and the sum of insulin was decreased during intravenous glucose tolerance test in the cancer patients. The elimination rate of glucose (k-value) during glucose challenge was, however, not significantly different in cancer patients as compared with that of appropriate controls. The activities of enzymes representative for glycogen turnover, glycolysis, citric acid cycle and respiratory chain were significantly lower in the muscle tissue of cancer patients, while the activity of 3-hydroxyacyl-CoA dehydrogenase, an enzyme in the beta-oxidation of fatty acids, was unchanged and the activity of glucose-6-phosphate dehydrogenase was significantly higher. Rate limiting enzyme activities in muscle tissue, phosphofructokinase and cytochrome c oxidase correlated signficantly with plasma insulin and glucose during glucose challenge. The results point at the possibility of covariating debilitation of pancreatic beta-cells and skeletal muscle enzymes caused by the malignant tumour.     

Fatty Acid Incorporation into Human Adipose Tissue in Hypertrigiyceridaemia*

The fatty acid and glucose incorporation into glycerides and glycerol release from adipose tissue were determined in a middle-aged population of 109 men and 41 women. 43 men and 19 women were rrormolipidaemic. The same analysis was also carried out in 13 male and 9 female normolipidaemic students. Needle biopsy specimens of adipose tissue were incubated in vitro in an albumin medium containing ³H-fatty acids and ¹⁴C-glucose. After two hours of incubation values for fatty acid and glucose incorporation were calculated from the incorporation of ³H-activity into the fatty acids and ¹⁴C-activity into the glycerol moiety of extracted glycerides. The mean values for fatty acid incorporation were lower in all types of hypertriglyceridaemic subjects (II B, III, IV and V) than in the normolipidaemic control subjects. In the male hypertriglyceridaemic population 36 % had values for fatty acid incorporation below the 5th percentile of the normolipidaemic group and 14 % had values below the lowest normal value. The rate of fatty acid incorporation was negatively correlated with the serum triglyceride concentration. This correlation remained unchanged when partial correlation was performed when the influence of body weight was eliminated. Fatty acid and glucose incorporation correlated positively. Incorporation of glucose behaved in the same way as described above for incorporation of fatty acids. Glycerol and fatty acid release was the same in the normo- and hypertriglyceridaemic groups. It is likely that the removal of plasma triglycerides from blood requires hydrolysis of triglycerides to fatty acids and the subsequent removal of the fatty acids. The hypothesis has been formulated that when the former process is normal, a defect of fatty acid removal (a low rate of fatty acid incorporation into glycerides) may be responsible for an impaired removal of plasma triglyceride-fatty acids. A low rate of fatty acid incorporation may contribute to the development of hypertrigiyceridaemia, according to this hypothesis.     

Relationship between the coenzyme A and the carnitine pools in human skeletal muscle at rest and after exhaustive exercise under normoxic and acutely hypoxic conditions.

Skeletal muscle CoA and carnitine metabolism were investigated in six human volunteers at rest and after exhaustive exercise under normoxic and hypoxic conditions. In comparison to the values at rest, exhaustive exercise was associated with a three- to fourfold increase in the skeletal muscle lactate, and with a twofold increase in the acetyl-CoA content, both under normoxic and hypoxic conditions. Since exercise did not significantly affect the skeletal muscle CoA radical (CoASH), total acid-soluble, or total CoA contents, the increase in the acetyl-CoA content was at the expense of short-chain acyl-CoAs different from acetyl-CoA. With exhaustive exercise, the skeletal muscle acetylcarnitine and short-chain acylcarnitine contents increased by a factor of three to four both under normoxic and hypoxic conditions. In contrast to the CoA pool, these increases were associated with a decrease in the free carnitine content, whereas the total acid-soluble and total carnitine contents were not affected by exercise. After exhaustive exercise, the skeletal muscle acetyl-CoA/CoASH ratio showed a linear correlation with the corresponding acetylcarnitine/free carnitine ratio. The plasma short-chain acylcarnitine concentration increased by a factor of two to three during exercise, and was not significantly different from the values at rest 40 min after completion of exercise. Thus, the current studies illustrate the close interaction between the CoA and carnitine pools in the exercising human skeletal muscle, and they underscore the important role of carnitine in maintaining the muscular CoASH content during exhaustive exercise.     

Kinetic compartmental analysis of carnitine metabolism in the human carnitine deficiency syndromes. Evidence for alterations in tissue carnitine transport.

The human primary carnitine deficiency syndromes are potentially fatal disorders affecting children and adults. The molecular etiologies of these syndromes have not been determined. In this investigation, we considered the hypothesis that these syndromes result from defective transport of carnitine into tissues, particularly skeletal muscle. The problem was approached by mathematical modeling, by using the technique of kinetic compartmental analysis. A tracer dose of L-[methyl-3H]carnitine was administered intravenously to six normal subjects, one patient with primary muscle carnitine deficiency (MCD), and four patients with primary systemic carnitine deficiency (SCD). Specific radioactivity was followed in plasma for 28 d. A three-compartment model (extracellular fluid, muscle, and "other tissues") was adopted. Rate constants, fluxes, pool sizes, and turnover times were calculated. Results of these calculations indicated reduced transport of carnitine into muscle in both forms of primary carnitine deficiency. However, in SCD, the reduced rate of carnitine transport was attributed to reduced plasma carnitine concentration. In MCD, the results are consistent with an intrinsic defect in the transport process. Abnormal fluctuations of the plasma carnitine, but of a different form, occurred in MCD and SCD. The significance of these are unclear, but in SCD they suggest abnormal regulation of the muscle/plasma carnitine concentration gradient. In 8 of 11 subjects, carnitine excretion was less than dietary carnitine intake. Carnitine excretion rates calculated by kinetic compartmental analysis were higher than corresponding rates measured directly, indicating degradation of carnitine. However, we found no radioactive metabolites of L-[methyl-3H]carnitine in urine. These observations suggest that dietary carnitine was metabolized in the gastrointestinal tract.     

Malonyl coenzyme A and the regulation of functional carnitine palmitoyltransferase-1 activity and fat oxidation in human skeletal muscle

Physiological hyperglycemia with hyperinsulinemia reduces fat oxidation in skeletal muscle. The mechanism responsible for this decrease in fat oxidation in human muscle is not known and may contribute to the development of insulin resistance. We hypothesized that the transfer of long-chain fatty acids (LCFAs) into the mitochondria via carnitine palmitoyltransferase-1 (CPT-1) is inhibited by increased malonyl coenzyme A (malonyl-CoA) (a known potent inhibitor of CPT-1) in human muscle during hyperglycemia with hyperinsulinemia. We studied six healthy subjects after an overnight fast and during an induced 5-hour period of hyperglycemia with hyperinsulinemia. Muscle fatty acid oxidation was calculated using stable isotope methodology combined with blood sampling from the femoral artery and vein of one leg. Muscle functional CPT-1 activity was assessed by concurrently infusing an LCFA tracer and a CPT-independent medium-chain fatty acid tracer. Muscle biopsies were obtained from the vastus lateralis after the periods of fasting and hyperglycemia with hyperinsulinemia. Hyperglycemia with hyperinsulinemia decreased LCFA oxidation, but had no effect on LCFA uptake or medium-chain fatty acid oxidation across the leg. Malonyl-CoA concentration significantly increased from 0.13 +/- 0.01 to 0.35 +/- 0.07 nmol/g during hyperglycemia with hyperinsulinemia. We conclude that hyperglycemia with hyperinsulinemia increases malonyl-CoA, inhibits functional CPT-1 activity, and shunts LCFA away from oxidation and toward storage in human muscle.     

Effects of nicotinic acid treatment on glyceride formation and lipolysis in adipose tissue of hyperlipidemic patients

Summary Thirty-one weight-stable patients with different types of hyperlipoproteinemia were treated daily with 4g nicotinic acid for 6 weeks. Effects of this therapy on adipose tissue metabolism were evaluated. By using biopsy specimens of subcutaneous adipose tissue, fatty acid and glucose incorporation into adipose tissue glycerides were measured in vitro as well as glycerol and fatty acid release, which allowed us to estimate adipose tissue lipolysis. The amount of fatty acids produced by lipolysis and thereafter utilized within adipose tissue without being released (fatty acid retention) was estimated. Fatty acid and glucose incorporation into adipose tissue, glycerol release and fatty acid retention values increased, but serum triglyceride levels decreased (allP<0.001) after nicotinic acid treatment. The change in fatty acid incorporation was positively correlated with changes in glucose incorporation into adipose tissue (r=0.53,P<0.01) and fatty acid retention (r=0.76,P<0.001). Although adipose tissue lipolysis, measured as glycerol release, increased, the lipolyzed fatty acids were retained in adipose tissue, suggesting an enhanced synthesis of glycerides both from exogenous and endogenous sources. The increase in fatty acid incorporation into adipose tissue indicates that the decrease in serum triglyceride levels produced by nicotinic acid treatment may partly be due to the fact that this drug promotes incorporation of fatty acids, derived from lipoprotein-carried triglycerides in the blood, into adipose tissue glycerides.     

Carnitine metabolism in early stages of Duchenne muscular dystrophy

Muscle carnitine deficiency was found in 12 children affected with Duchenne muscular dystrophy (DMD), the diagnosis being made at a preclinical stage or at the beginning of the clinical symptoms. Enzymatic activities related to fatty acid transport and carnitine metabolism were studied in these patients and normal subjects: palmitoyl carnitine transferase was increased, palmitoyl carnitine hydrolase was not found in the muscle, palmitoyl coenzyme A synthetase was normal and palmitoyl coenzyme A hydrolase was increased.     

Mechanism of increased tolerance to hypothermia after composite Indian herbal preparation II administration

OBJECTIVE: Investigation of the mechanism of increased tolerance to stress induced hypothermia after the administration of composite Indian herbal preparation II (CIHP II), a combination of several plant ingredients and minerals. DESIGN: The effect of oral CIHP II administration (1 mg/g of body weight), prior to cold (5 degrees C)-hypoxia (428 mm Hg)-restraint (C-H-R) exposure in rats on cardiac and skeletal muscle oxidation was studied in vitro by estimating conversion of glucose-U-14C and Palmitate-1-(14)C to 14CO2. In vitro adipose tissue lipolysis and incorporation of glucose-U-14C into skeletal muscle glycogen was also studied. RESULTS: A single dose of CIHP II-enhanced resistance to hypothermia (rectal temperature [T(rec)] 23 degrees C) during C-H-R exposure as evidenced by increased glucose turnover rate in heart and skeletal muscle tissue. The blood glucose and skeletal muscle glycogen were conserved. Cardiac free fatty acid oxidation was also increased. During recovery from hypothermia (T(rec) 37 degrees C) blood glucose and muscle glycogen levels were conserved. Five doses of CIHP II increased resistance to cold by increased adipose fat mobilization and cardiac oxidation. Glucose oxidation was spared. During recovery from hypothermia, the glucose turnover and oxidation in skeletal muscle was increased as was fat mobilization from adipose tissue and its oxidation by heart muscle. CONCLUSIONS: CIHP II intake prior to C-H-R exposure resulted in increased glucose turnover rate and fat utilization. This perhaps helped increase the resistance to C-H-R-induced hypothermia and speeded recovery.     

Internal redistribution of tissue protein synthesis in uremia

Tissue composition and in vivo tissue protein synthesis were altered by acute uremia, induced in rats by bilateral nephrectomy. Net protein synthesis (anabolism minus catabolism) was increased in liver and heart and decreased in skeletal muscle, as judged from changes in total organ weight, ratios of protein: DNA and RNA: DNA, and leucine-(14)C incorporation into trichloroacetic acid (TCA)-insoluble, nucleic acid-free material. Concentration of free lysine, a major constituent of histones and ribonucleoproteins, also was increased in liver and decreased in skeletal muscle, a finding suggesting lysine shifted from muscle to liver in association with the changes in protein synthesis. Acute uremia also altered tissue levels of other amino acids. Hepatic concentrations and liver:blood concentration ratios tended to be increased for the essential, but not for the nonessential amino acids. Moreover, the phenylalanine:tyrosine concentration ratio, which reflects activity of the enzyme phenylalanine hydroxylase, was increased in blood, muscle, and liver. These findings indicate uremia selectively alters tissue composition and protein synthesis in different organs and may modify intermediary metabolism of some individual amino acids.     

Secondary carnitine deficiency

For any given tissue the normal carnitine content is that which is necessary for an optimal rate of long-chain fatty acid oxidation. Tissues especially rich in carnitine are liver, muscle and heart. The endogenous rate of carnitine biosynthesis from lysine and methionine is not known to be influenced by fluctuations in the levels of the parent amino acids, as exemplified by hypermethioninaemic patients. Inadequate dietary supply of carnitine, leading to a deficiency, may occur in vegetarians and especially in subjects on total parenteral nutrition. Premature babies are especially at risk in this respect, and this has led to the addition of carnitine to solutions for intravenous alimentation. It has been suggested that carnitine plays an important role in the intramitochondrial regulations of coenzyme A homeostasis by expelling short-chain and medium-chain acyl groups from the mitochondrion in the form of acylcarnitines. These esters are preferentially excreted into the urine and thus result in a depletion of the body's carnitine stores. Important conditions in this respect are the inherited organic acidurias and disorders of fatty acid oxidation. Urinary acylcarnitines can be identified by indirect gas chromatographic or direct mass spectrometric methods. Patients on haemodialysis treatment will lose carnitine in the dialysis fluid, whereas excessive urinary losses of free and acetylated carnitine occur in the Fanconi syndrome. Secondary carnitine deficiency may be accompanied by a moderate degree of muscular dysfunction. Reassuringly, however, no signs of hepatic or cardiac involvement, as often seen in primary carnitine deficiency, have been observed.     

A micro-method for determination of fatty acid (FIAT) and glucose (GLIAT) incorporation and lipolysis in vitro in needle biopsies of human adipose tissue.

A method for determination of fatty acid (FIAT) and glucose (GLIAT) incorporation into adipose tissue in vitro in needle biopsy specimens of human fat has been developed. 20-150 mg of subcutaneous fat is incubated in an albumin buffer containing a physiological spectrum and concentration of fatty acids and glucose. Release of glycerol and fatty acids to the incubation medium and incorporation of labelled palmitic acid and labelled glucose into extracted adipose tissue lipids are determined simultaneously. The labelled fatty acids are found in the fatty acid part and the labelled glucose only in the glycerol part of extracted diglycerides and triglycerides. These glycerides are completely recovered and indicated FIAT and GLIAT values. Methodological errors for all vaiables are about 10%. All processes increase linearly with tissue weight and incubation time. FIAT and GLIAT increase linearly with increasing concentration of a physiological spectrum of fatty acids (=constant fractional incorporation). The method is simple, and several analyses from one subject can be performed on one day with a minimum of discomfort to the patient.     

Defective lipid metabolism in the failing heart

The metabolism of long chain fatty acids was investigated in the failing heart of guinea pigs with chronic constriction of the ascending aorta. Homogenates prepared form failing hearts exhibited (a) a decreased capacity to oxidize palmitic acid (failure = 0.50 +/- 0.06 mumole/g of protein per 20 min; control = 1.09 +/- 0.10); (b) a reduced level of carnitine, a myocardial constituent which serves to control the oxidation rate of long chain fatty acids in the heart (failure = 0.91 +/- 0.10 mumole/g wet weight; control = 1.69 +/- 0.10); and (c) an increased rate of palmitate incorporation into triglycerides and lecithin. Exogenous carnitine effected a restoration of the defective palmitate metabolism of the homogenates towards normal. In contrast to long chain fatty acid oxidation, glucose oxidation by the failing heart was not impaired. As a consequence of this selective lesion in energy substrate utilization, the failing heart might be forced to rely on substrates other than long chain fatty acids for its major energy supply.     

Levo-carnitine, its derivatives, and free fatty acids in serum, heart, liver, and muscle of both tumoral and alcoholic rats

We present a comparative study of carnitine-related fatty acid metabolism in rats bearing a Yoshida sarcoma, in chronic alcoholic rats, and in control rats. Levels of levo-carnitine, acetylcarnitine, acylcarnitine, and free fatty acids were studied in serum and in different tissues--liver, heart, and skeletal muscle--of each group of rats. Chronic alcoholic rats showed high levels of free fatty acids and elevated levo-carnitine and acetylcarnitine levels relative to those of the controls. Biosynthesis of carnitine appeared to be increased, whereas fatty acid oxidation was depressed. Tumor-bearing rats also showed high levels of free fatty acids in both serum and tissues. However, levels of levo-carnitine were decreased in this group. It seems that the tumor not only utilizes the precursors of carnitine biosynthesis but also increases carnitine expenditure.