Modulation of leucine oxidation and turnover by graded amounts of carbohydrate intake in obese subjects

Our previous in vitro studies with rat tissues have suggested that ketone bodies may regulate the oxidation of branched-chain amino acids. To investigate the physiological and clinical significance of this observation, we determined the effect of starvation-induced ketosis on leucine metabolism in obese subjects. Rates of turnover, plasma clearance, and expiratory ¹⁴CO₂ production (indicator of oxidation) after intravenous infusion of a trace amount of [1-¹⁴C]-leucine were measured before and one week after starvation (80 cal/day). This dietary treatment caused a significant increase in the rate of ¹⁴CO₂ production, but significantly reduced the turnover (9.1 versus 7.0 mmole/hr) and plasma clearance (65 versus 34 L/hr) of leucine. When ketosis was prevented by a daily intake of 300 calories of carbohydrate, the rate of ¹⁴CO₂ production was significantly decreased. On the other hand, starvation-induced decreases in turnover and plasma clearance of leucine, increases in plasma concentrations of branched-chain amino acids (marker for heightened proteolysis), decreases in plasma concentrations of alanine (marker for stimulated hepatic gluconeogenesis), and decreases in plasma concentrations of glucose and insulin were not prevented until carbohydrate intake was increased to 500 or 800 calories per day. Increases in daily carbohydrate intake (up to 500 calories) were accompanied by decreases in urinary excretion of nitrogen, but not 3-methylhistidine (marker for muscle proteolysis). Our data suggest that: (1) ketosis directly or indirectly enhances oxidation of leucine, (2) starvation-induced ketosis, proteolysis, and gluconeogenesis can be prevented sequentially by carbohydrate diets providing fro 300–800 calories per day, (3) the reduced turnover of leucine in starvation is most likely the result of reduced protein synthesis, and (4) diminution of branched-chain amino acid catabolism is a component of the nitrogen-sparing effect of carbohydrate.     

Effects of dietary substitution of mixed amino acids for glucose on the splanchnic metabolism of plasma triglycerides, cholesterol, carbohydrates, and amino acids in conscious fed baboons

Splanchnic metabolism was studied in the fed state during prolonged constant intravenous administration of tracer amounts of [9,10]-3H palmitic acid and the calculated isocaloric intraduodenal administration (13 mg/min X kg body wt0.75) of either (1) glucose, (2) 15% mixed amino acids and 85% glucose or (3) 45% mixed amino acids and 55% glucose to conscious, restrained female baboons that had been maintained on a similar diet (supplemented in essential nutrients) for the previous 9 days. Secretion of plasma triglycerides from the splanchnic region was quantified from splanchnic flow and radiochemical measurements of transsplanchnic gradients of 3H-labeled free fatty acids and triglycerides. Mean splanchnic secretion of plasma triglycerides increased significantly as the proportion of dietary calories derived from amino acids was varied from 0 to 15 to 45% (mean values 1.1 +/- 0.1, 2.6 +/- 0.2 and 4.2 +/- 0.3 mumol/min kg body wt0.75, respectively, p less than 0.05). Increased triglyceride secretion was attributable to both significantly higher rates of esterification of free fatty acids taken up in the splanchnic region to triglycerides released into hepatic venous blood plasma (mean values 10 +/- 1, 16 +/- 2 and 34 +/- 5%, respectively) and to significantly higher rates of secretion of triglycerides derived from precursors other than free fatty acids. Higher intake of amino acids was also associated with both higher plasma concentrations of cholesterol and higher values for hepatic oxidation of cholesterol to bile acids.(ABSTRACT TRUNCATED AT 250 WORDS)     

Partial substitution of amino acids of a parenteral solution with tripeptides: Effects on parameters of protein nutrition in baboons

We previously showed that triglycine and trileucine are efficiently utilized when infused intravenously (IV) in baboons who are fed a complete diet orally. In the present experiments we investigated the utilization of these tripeptides in the context of total parenteral nutrition. A group of subhuman primates (baboon) was subjected sequentially to two forms of total parenteral nutrition, each for a period of six days. The only difference between the two periods was that in one, all amino acids were given in free form, and in the other, the glycine and leucine components of the amino acid mixture were replaced with triglycine and trileucine, respectively. During both experimental periods the infusion solution provided daily 100 calories/kg body weight and 2.5 g amino acids/kg body weight. There were no significant differences between nitrogen balance, plasma amino acid concentrations, or urinary excretion of amino acids for the two forms of parenteral nutrition. The only exceptions were a greater plasma concentration of isoleucine and a greater urinary excretion of leucine during infusion of the partial peptide solution. Assimilation of triglycine and trileucine under the conditions of total parenteral nutrition was assessed by determining concentrations of these peptides in plasma and urine. Trileucine was not found in plasma, and only 1.8% of the amount of trileucine infused appeared as trileucine and dileucine in urine. Triglycine was detected in plasma and 17.1% of the amount of triglycine infused was excreted in urine as triglycine and diglycine. These data suggest that assimilation of trileucine and triglycine under the conditions of our experiment was sufficiently efficient to meet the daily need for an essential amino acid (leucine) and for nitrogen (glycine).     

Low dose leptin administration reverses effects of sustained weight-reduction on energy expenditure and circulating concentrations of thyroid hormones

Maintenance of a reduced body weight is associated with decreased 24-hour energy expenditure, and decreased circulating concentrations of leptin and thyroid hormones. To determine whether these adaptive metabolic and endocrine changes are partly leptin-mediated, we measured body composition, aspects of energy expenditure, and circulating concentrations of leptin and thyroid hormones in 4 subjects at 3 time points: 1.) Usual body weight; 2.) While stable at 10% reduced body weight; and 3.) During a 5-week period at 10% reduced body weight while receiving twice per day leptin injections that restored 8 AM circulating leptin concentrations to those seen at usual body weight. During maintenance of a 10% reduced body weight, circulating T3, T4, and leptin concentrations were decreased. All of these endocrine changes were reversed by administration of "replacement" doses of leptin (r-metHuLeptin). Indirect calorimetry, and subtle changes in body composition associated with leptin administration, were used to calculate the net change in stored calories and in 24-hour energy expenditure. Total energy expenditure increased in all subjects during r-metHuLeptin administration. These data indicate that decrease leptin concentrations resulting from loss of fat mass account for some aspects of the endocrine/metabolic phenotype associated with the weight-reduced state.     

Starvation in man.

Starvation entails a progressive selection of fat as body fuel. Soon after a meal glucose utilisation by muscle ceases and fatty acids are used instead. Ketoacid levels in blood become elevated over the first week, and the brain preferentially uses these instead of glucose. The net effect is to spare protein even further, as glucose utilisation by brain is diminished. Nevertheless, there is still net negative nitrogen balance, but this can be nullified by amino acid or protein supplementation. Insulin appears to be the principal regulatory hormone. Recent data suggest that decreased levels of active T3 may play a role by sparing otherwise obligated calories by decreasing metabolic needs.     

Spontaneous and experimental human obesity: effects of diet and adipose cell size on lipolysis and lipogenesis.

We examined the hypothesis that adipose tissue from lean and obese subjects might provide different internal signals in response to changes in stored calories. Adipose tissue was obtained before weight gain in nonobese subjects and after weight gain in five of the same individuals. Adipose tissue was removed before and after weight loss in seven obese patients. Two isocaloric diets were fed to both groups for 2–3 wk each; one diet was high in carbohydrate, and the other contained a low carbohydrate content. Incorporation of radioactivity from pyruvate into fatty acids in vitro was lower with the low-carbohydrate diet than with the high-carbohydrate diet. It was also significantly reduced after weight gain in the nonobese subjects but was not significantly altered in the obese. There were no significant effects of diet or weight gain on the enzymatic activities in the nonobese subjects. The large fat cells from both groups of subjects had an increased sensitivity to the lipolytic effects of isoproterenol as compared with the smaller fat cells. Variations in carbohydrate intake had no effect on the lipolytic response to isoproterenol. The dose response of fat cells to dibutyryl-cyclic-3′,5′-AMP did not change after weight gain in the nonobese males, but was significantly reduced on both levels of carbohydrate after weight loss in the obese (i.e., when studying the smaller fat cells). These studies suggest that differences in the metabolism of adipose tissue between obese and lean subjects persist when differences in the size of fat cells and caloric intake are controlled.     

Saturated fat intake and insulin resistance in men with coronary artery disease. The Stanford Coronary Risk Intervention Project Investigators and Staff

BACKGROUND. To determine whether there is an association between diet and plasma insulin concentration that is independent of obesity, we studied the relation of dietary composition and caloric intake to obesity and plasma insulin concentrations in 215 nondiabetic men aged 32-74 years with angiographically proven coronary artery disease. METHODS AND RESULTS. After adjusting for age, the intake of saturated fatty acids and cholesterol were positively correlated (p less than 0.05) with body mass index (r = 0.18, r = 0.16), waist-to-hip circumference ratio (r = 0.21, r = 0.22), and fasting insulin (r = 0.26, r = 0.23). Carbohydrate intake was negatively correlated with body mass index (r = -0.21), waist-to-hip ratio (r = -0.21), and fasting insulin (r = -0.16). Intake of monounsaturated fatty acids did not correlate significantly with body mass index or waist-to-hip circumference ratio but did correlate positively with fasting insulin (r = 0.24). Intake of dietary calories was negatively correlated with body mass index (r = -0.15). In multivariate analysis, intake of saturated fatty acids was significantly related to elevated fasting insulin concentration independently of body mass index. CONCLUSIONS. These cross-sectional findings in nondiabetic men with coronary artery disease suggest that increased consumption of saturated fatty acids is associated independently with higher fasting insulin concentrations.     

Obesity an overview: Genetic conditions and recent developments in therapeutic interventions

Obesity is a complex disorder that is linked to many coexisting disorders. Recent epidemiological data have suggested that the prevalence of obesity is at an all-time high, growing to be one of the world's biggest problems. There are several mechanisms on how individuals develop obesity which includes genetic and environmental factors. Not only does obesity contribute to other health issues but it also greatly affects the quality of life, physical ability, mental strength and imposes a huge burden in terms of healthcare costs. Along with that, obesity is associated with the risk of mortality and has been shown to reduce the median survival rate. Obesity is basically when the body is not able to balance energy intake and output. When energy intake exceeds energy expenditure, excess calories will be stored as fat leading to weight gain and eventually obesity. The therapeutic market for treating obesity is composed of many different interventions from lifestyle intervention, surgical procedures to pharmacotherapeutic approaches. All of these interventions have their respective benefits and disadvantages and are specifically prescribed to a patient based on the severity of their obesity as well as the existence of other health conditions. This review discusses the genetic and environmental causes of obesity along with the recent developments in anti-obesity therapies.     

Six-month patient outcomes in a preventive cardiology center

More effective ways to improve lifestyle behaviors need to be developed. Two hundred forty adult patients at a preventive cardiology clinic were randomly assigned to receive either one or five sessions of behavioral instruction to improve cardiovascular risk behaviors. Results for 102 patients from 6-month follow-up data revealed few significant differences between the two groups. However, in the two groups combined, there were significant reductions in total calories, percent of calories from total fat, percent of calories from saturated and monounsaturated fat, and dietary cholesterol. Reductions were also found in systolic blood pressure, triglycerides, body mass index, and weight. In multiple regression analyses, changes in physiologic variables were primarily associated with baseline and demographic characteristics. Changes in total calories, percent of calories from polyunsaturated fat, and walking were predicted by changes in social support or knowledge. Although most patients improved, the intensity of behavior change instruction was not related to the amount of change in cardiovascular risk factors.     

Increase of microsomal glucose-6-phosphatase activity after chronic ethanol administration

To study the effect of chronic ethanol administration on the activity of hepatic microsomal glucose-6-phosphatase, female rats were pair-fed liquid diets with 36% of total calories either as ethanol or isocaloric carbohydrate (controls). The remainder of the diet contained 35% of total calories as fat, 18% as protein, and 11% as additional carbohydrate. Six weeks of ethanol feeding as isocaloric substitution for carbohydrate increased significantly the activity of glucose-6-phosphatase (expressed per mg microsomal protein) both in fed (38%; p < 0.001) and fasted 18%; p < 0.02) rats. When expressed per unit of body weight, the enzyme activity was increased even further both in fed (66%; p < 0.01) and fasted (43%; p < 0.01) rats. Another group of rats received diets containing 36% of calories either as ethanol or isocaloric fat. The remainder of the diet contained 11% of total calories as carbohydrate, 18% as protein, and 35% as additional fat. Six weeks of this ethanol feeding as isocaloric substitution for fat again increased glucose-6-phosphatase activity significantly. Ultracentrifugation in a Cs⁺-containing sucrose gradient to separate rough and smooth microsomes revealed that the increase in glucose-6-phosphatase activity after ethanol feeding occurred mainly in the smooth microsomal membranes.     

Whole body protein turnover,studied with 15N-glycine,and muscle protein breakdown in mildly obese subjects during a protein-sparing diet and a brief total fast

A modification of the Picou and Taylor-Roberts Model was used to estimate rates of total body protein synthesis (S), breakdown (C), and amino nitrogen (N) flux (Q) in the metabolic N pool of five obese females. The subjects were fed egg white albumin at 1.5/kg ideal body weight (IBW) and total calories at 1.2 times the basal energy expenditure (fat:carbohydrate = 30%:50%) as a formula diet (period 1, 1 wk). This was followed by 3 wk during which the nonprotein calories were omitted (period 2, protein-sparing modified fast [PSMF]) and a 1-wk total fast (period 3). Estimates of body protein turnover and skeletal protein breakdown were made during the last 60 and 48 hr, respectively, of each period. Q, S, and C were 223 ± 22, 154 ± 22, and $\text{150 ± 22 g protein}\text{24 hr}$, respectively, for period 1. These values were unchanged at the end of period 2. Total fasting decreased Q and S by 36% and 27%, respectively (p < 0.001), but C remained unchanged. Skeletal protein breakdown, as estimated by urinary Nτ-methylhistidine excretion, was 108 ± 47 μmole in period 1, 79 ± 51 μmole in period 2 (p < 0.01), and 100 ± 49 μmole in period 3, representing 16 ± 5%, 12 ± 5% (p < 0.01), and 16 ± 4% of whole body breakdown. N balance was unchanged in period 1 (?0.4 ± 1.2 g N) and the final week of period 2 (?0.4 ± 1.5 g N), but was ?5.8 ± 0.6 g N in period 3. These data indicate that weight reduction with a PSMF is associated with a maintenance of total body protein turnover parameters and N balance but a reduction in skeletal protein breakdown, whereas a total fast causes a marked reduction in whole body protein synthesis and amino N flux with little change in the rate of total body and skeletal protein breakdown, resulting in a negative N balance. The minimization of N losses that develops after prolonged starvation is achieved at rates of whole body and skeletal protein breakdown similar to those found when the diet is adequate, suggesting that endogenous fat-derived fuels are as effective as exogenous energy in limiting protein catabolism. However, protein intake is necessary to maintain whole body protein synthesis under these conditions.     

Effects of medium-chain triglyceride feeding on energy balance in adult humans

In recent years, the metabolism of triglycerides has attracted much attention. Oxidation of fatty acids is an essential energy supply, especially when glucose supply is limited. In the present study, the effect of a 3-day high medium-chain triglyceride (MCT; 51% of calories), low carbohydrate intake on plasma glucose and amino acid, and urinary organic acid levels, including dicarboxylic and tricarboxylic acid cycle intermediates, was determined in eight normal adult volunteer subjects. Urine was collected at baseline and at 48 to 72 hours for amino acid and organic acid levels, and plasma collected at 0 and 72 hours for glucose and amino acid concentration. The MCT diet increased urinary levels of dicarboxylic acids (adipic 8-, suberic 65-, sebacic 284-fold) and keto acids (acetoacetate and beta-hydroxybutyrate, 67.5-fold); alanine and lactate were decreased 2.5- and 4-fold, respectively, while pyruvate, other amino acids and citric acid intermediates remained unchanged. Plasma amino acid levels were unchanged, while the plasma glucose levels decreased by 8% from baseline. The loss of calories as urinary dicarboxylic acids and keto acids, although increased during the MCT diet, was less than 1% of the daily caloric intake. The data suggest MCT sustain energy expenditure through medium-chain fatty acid (MCFA) oxidation with no decrease in citric acid cycle intermediates, while sparing protein oxidation.     

Consistent relationships between sensory properties of savory snack foods and calories influence food intake in rats

OBJECTIVE: Determine the influence of experience with consistent or inconsistent relationships between the sensory properties of snack foods and their caloric consequences on the control of food intake or body weight in rats. DESIGN: Rats received plain and BBQ flavored potato chips as a dietary supplement, along with ad lib rat chow. For some rats the potato chips were a consistent source of high fat and high calories (regular potato chips). For other rats, the chips provided high fat and high calories on some occasions (regular potato chips) and provided no digestible fat and fewer calories at other times (light potato chips manufactured with a fat substitute). Thus, animals in the first group were given experiences that the sensory properties of potato chips were strong predictors of high calories, while animals in the second group were given experiences that the sensory properties of potato chips were not predictors of high calories. SUBJECTS: Juvenile and adult male Sprague-Dawley rats. MEASUREMENTS: Following exposure to varying potato chip-calorie contingencies, intake of a novel, high-fat snack food and subsequent chow intake were assessed. Body weight gain and body composition as measured by DEXA were also measured. RESULTS: In juvenile animals, exposure to a consistent relationship between potato chips and calories resulted in reduced chow intake, both when no chips were provided and following consumption of a novel high-fat, high-calorie snack chip. Long-term experience with these contingencies did not affect body weight gain or body composition in juveniles. In adult rats, exposure to an inconsistent relationship between potato chips and calories resulted in increased consumption of a novel high-fat, high-calorie snack chip premeal along with impaired compensation for the calories contained in the premeal. CONCLUSION: Consumption of foods in which the sensory properties are poor predictors of caloric consequences may alter subsequent food intake.     

Energetic and metabolic studies of intragastric infusion of calories before and after exercise training

The technique of intragastric infusion of calories was used to examine the energetics and metabolic response to fasting, feeding and overfeeding states in adult, sedentary subjects. All subjects were studied before and after participating in a 12-week aerobic exercise training program that increased maximum aerobic capacity by an average of 15.6 percent. Body weight did not change during the exercise program, but there was a slight and statistically significant increase in fat-free mass and a significant decrease in fat mass. The exercise program did not affect food intake (as determined from food records). When subjects were studied before exercise training, there was no increase in energy expenditure above fasting levels during continuous infusion of calories at a rate near the subject's maintenance energy requirements. When infusion rate was increased to twice maintenance, energy expenditure increased significantly and produced a measurable thermic effect of food. The changes in glucose, insulin and free fatty acids did not parallel the changes in energy expenditure, but changes in lactate levels did. Moreover, there were some gender differences in the pattern of substrate and hormone changes with changes in feeding state. Exercise training did not alter either energy expenditure or the pattern of changes in substrates and hormones with changes in feeding state. In summary, the exercise program led to changes in body composition without measurable changes in either food intake (assessed from diet records) or energy expenditure (assessed during fasting and continuous infusion of calories). The change in body composition must have been due to either (1) the energy cost of the exercise itself, or (2) changes in the substrates used for oxidation, either during or following exercise bouts. We conclude that exercise, unlike food restriction, can lead to changes in body composition without altering body weight or metabolic rate, and can contribute to the acquisition and maintenance of a desirable body weight and composition.     

Vigorous supplementation of a hypocaloric diet prevents cardiac arrhythmias and mineral depletion

We have previously demonstrated that a hypocaloric, nutritionally deficient, liquid protein diet is associated with potentially lifethreatening cardiac arrhythmias, which increased in frequency and complexity over the duration of the study. The present investigation was designed to evaluate the metabolic and cardiac changes associated with a hypocaloric, but otherwise nutritionally complete, diet. Six healthy, obese females from 154 to 182 percent of ideal body weight were evaluated in a metabolic ward for 48 days. The subjects ingested a weight maintenance diet during an eight-day period, which was followed by 40 days of an experimental diet containing 472 kcal of a mixture of protein (60 percent of calories), carbohydrate (25 percent), and fat (15 percent). This diet equaled or exceeded the recommended daily allowances for minerals, trace elements, vitamins, and essential fatty acids. The subjects were monitored for balances of nitrogen and minerals, as well as for the appearance of cardiac arrhythmias by 24-hour electrocardiographic recordings. Nitrogen balance was positive, and the previously demonstrated negative balances for potassium, sodium, calcium, magnesium, and phosphorus were either reversed or markedly decreased. In contrast to our previous study, no arrhythmias were observed in subjects ingesting the present experimental diet, and no significant change in cardiac rhythm was found in 13 obese, but otherwise healthy, outpatients. The data, based on a limited number of subjects, suggest that a hypocaloric diet vigorously supplemented with essential elements, micronutrients, and vitamins appears to be safer than the once popular, incomplete liquid protein preparation.     

Molecular physiology of syndromic obesities in humans.

Obesity has become an increasingly prevalent public health problem and represents the complex interaction of genetic, developmental, behavioral and environmental influences. Although rare, the study of syndromic forms of obesity provides insight into underlying molecular and physiological mechanisms by which adiposity is regulated through food intake, energy expenditure and partitioning of stored calories.     

Whole-body protein synthesis and breakdown rates in children before and after reconstructive surgery of the skin.

The effects of minor surgery on dynamic aspects of whole-body nitrogen metabolism were explored in healthy children aged 4--15 yr. A continuous administration of 15N-glycine was used to estimate rates of whole-body protein synthesis and breakdown both before reconstructive surgery of the skin and 5 days afterward. Mean preoperative values for protein synthesis and protein breakdown were 3.9 and 3.4 g protein/kg body weight/day, respectively. Protein synthesis decreased by 15% (p less than 0.05) postoperatively, but body weight, intake of protein and calories, nitrogen balance, and protein breakdown did not differ significantly between the two periods. Protein synthetic rate correlated (p less than 0.05) with protein (r = +0.75) and calorie (r = +0.58) intake. These results indicate that minor surgery causes a small decrease in the rate of whole-body protein synthesis even though calorie and nitrogen balance are maintained.     

The comparative reductions of the plasma lipids and lipoproteins by dietary polyunsaturated fats: Salmon oil versus vegetable oils

The lower plasma lipid levels and lower incidence of atherosclerotic diseases in Greenland Eskimos suggested that the unusual fatty acids present in their diet of seal and fish may be anti-atherogenic. These fatty acids are eicosapentaenoic (C20:5) and docosahexaenoic (C22:6) acids and are of the omega-3 fatty acid family. We have compared a salmon oil diet containing high levels of these unique fatty acids to a control diet high in saturated fat and to a vegetable oil diet high in linoleic acid (C18:2). All diets contained 40% of the total calories as fat and 500 mg of cholesterol; they differed only in fatty acid composition. In 4 wk the salmon oil diet reduced plasma cholesterol levels from 188 to 162 mg/dl (p < 0.001) and triglyceride levels from 77 to 48 mg/dl (p < 0.005). LDL and VLDL cholesterol levels changed from 128 to 108 and 13 to 8 mg/dl (p < 0.005), respectively. HDL cholesterol levels did not change. The vegetable oil diet caused similar decreases in cholesterol levels but did not lower triglyceride levels. The omega-3 fatty acids comprised up to 30% of the total fatty acids in each plasma lipid class after the salmon diet. Fish oils contain fatty acids which may be metabolically unique and potentially useful in the control of both hypercholesterolemia and hypertriglyceridemia.     

Dietary therapy for different forms of hyperlipoproteinemia

Diet is the first line of therapy for hypercholesterolemia. The major dietary factors raising the plasma cholesterol are saturated fatty acids, cholesterol, and excess total calories. For almost all forms of hyperlipidemia, the first principle of dietary therapy is to reduce saturated fatty acids, decrease cholesterol, and curtail excess calories. In patients with severe hypercholesterolemia, marked restrictions of diet may be necessary. For these patients, drugs may be required to control cholesterol levels. However, the majority of patients with elevated plasma cholesterol can achieve a satisfactory reduction of cholesterol levels by diet, and drugs will not be necessary. Dietary therapy alone is adequate for most patients with familial forms of hypertriglyceridemia, but for a few patients drugs are required.     

Ethanol-Related Changes in Liver Microsomes and Mitochondria from the Monkey, Macaca fascicularis

Four Macaca fascicularis monkeys were maintained 1 year on a liquid diet containing 26% of calories as ethanol. Four control animals were fed a liquid diet of equivalent calories with protein, carbohydrate, and fat being substituted for ethanol calories. In liver mitochondria prepared from ethanol-fed monkeys (ethanol mitochondria), respiratory control was lowered 20% due to a decrease in state 3 respiration (28%). This was also accompanied by a 20% decrease in ADP translocation into ethanol mitochondria. The major change was a 61% decrease in cytochrome oxidase activity. The respiratory rate in the presence of uncoupler was also lowered 14%, but the decrease was not statistically significant. In contrast with our earlier observations with Macaca nemestrina, no significant ethanol-induced changes were observed in enzyme activities associated with the microsomal electron transport system, and no ethanol-elicited fatty liver was evident. The major changes in fatty acid composition of microsomal and mitochondrial phospholipids were increased amounts of palmitoleic and oleic acids, and decreased amounts of linoleic and arachidonic acids.