Metabolic Changes In Liver Research Articles

Metabolic control patterns in acute phase and regenerating human liver determined in vivo by 31-phosphorus magnetic resonance spectroscopy.

To elucidate the metabolic changes occurring within hepatocytes during acute phase reaction and liver regeneration. The metabolic events occurring within the liver during the hepatic stress response are poorly understood. The authors used in vivo 31-phosphorus magnetic resonance spectroscopy to study hepatic metabolism after surgical trauma with and without loss of liver cell mass. Three groups were studied: five patients undergoing partial hepatectomy; five patients in whom laparotomy and colonic resection was performed; and five patients treated by thyroidectomy. Hepatic metabolism was evaluated by 31-phosphorus magnetic resonance spectroscopy before surgery and serially thereafter on postoperative days 2, 4, 6, 14, and 28. Estimation of liver volume by magnetic resonance imaging and blood sampling for biochemistry were performed at the same time points. The authors found that alterations in hepatocyte phospholipid metabolism occurred after surgery that were correlated with changes in circulating acute phase proteins. Liver regeneration after hepatectomy was also associated with a derangement in energy metabolism, measured by a decrease in the ratio of ATP to its hydrolysis product inorganic phosphate. The depleted energy status was mirrored in biochemical indices of liver function, and restitution paralleled the course of restoration of hepatic cell mass. These findings indicate that changes in liver metabolism after surgery reflect the magnitude of tissue injury and the quantity of functioning liver cells. Acute phase responses dominate the initial recovery period at the expense of less important endergonic functions. When liver parenchyma is lost, the acute phase reaction is maintained and further supported by a rapid replenishment of hepatocytes, which can even be considered a continuation of acute phase physiology. Modulation of liver function within the framework of overall hepatic energy economy is one mechanism for matching energy supply with increased demands during these processes.

Biliary drainage for obstructive jaundice enhances hepatic energy status in humans: a 31-phosphorus magnetic resonance spectroscopy study.

Biliary obstruction impairs liver function although the pathophysiological mechanism is incompletely understood. The aim of this study was to examine serial changes in liver metabolism in patients with obstructive jaundice using image guided in vivo 31-phosphorus magnetic resonance spectroscopy ((31)P MRS). This technique allows repeated and non-invasive assay of organ energy metabolism and phospholipid biochemistry. We studied 10 patients presenting with obstructive jaundice secondary to extrahepatic localised malignancy. There were eight men and two women, median age 72 years (range 54-94), six with cholangiocarcinoma (all Bismuth type 1) and four with carcinoma of the head of the pancreas. Ten healthy volunteers (median age 24 years (range 21-26)) were studied for comparison. Hepatic metabolism in jaundiced patients was measured by (31)P MRS at presentation and again after a one week period of biliary drainage. Conventional liver function tests were also recorded. Compared with controls, liver spectra from jaundiced patients contained an excess of phosphomonoester (PME) metabolites (PME/total phosphate median 10.3% (interquartile range 8.7-11.5) in controls, 15.4% (13.1-17.7) in jaundiced cases; p<0.01). Biliary decompression was achieved in all patients (five with internal stents and five by external drainage catheters), and plasma biochemistry improved predictably (bilirubin 176 micromol/l (158-351) at presentation, 110 micromol/l (42-241) after drainage for one week; p<0.01). Enhancement of hepatic energy status, measured by the ratio of adenosine triphosphate (ATP) to inorganic phosphate (Pi), was observed in all cases after relief of biliary obstruction (ATP/Pi 1.4 (1.17-1.69) at presentation, 1.97 (1.4-2.48) after drainage; p<0.01) and was independent of the route of bile drainage. Hepatic phosphodiester (PDE) content was decreased after relief of obstruction (PDE/total phosphate 25.2% (20.5-27.4) at presentation, 19.8% (16.6-24.5) after drainage; p<0.01). This change was probably due to a reduction in the contribution from bile contents to this resonance as a strong PDE signal was also detectable in spectra obtained from separate bile specimens. Obstructive jaundice produces alterations in liver phosphoester biochemistry, most likely reflecting disturbances in phospholipid metabolism. Relief of biliary obstruction is associated with a measurable increase in hepatic energy status. Bile may contribute to the phosphodiester signal of the 31-phosphorus liver spectrum and changes in these resonances must therefore be interpreted with caution and in relation to the clinical situation. Monitoring of liver metabolism by (31)P MRS may allow clinicians to refine the selection and timing of therapeutic options in jaundiced patients.

Energy Metabolism in Fish Tissues Related to Osmoregulation and Cortisol Action

This is an overview of our recent studies of energy metabolism in fish brain and other organs regulated by exogenous (feeding, salinity) and endogenous (hormones) factors. To highlight our approach, we present latest results concerned osmoregulation in the gills of gilthead seabream, Sparus auratus. Our model, the seabream, is a euryhaline teleost capable of adaptation to extreme changes in environmental salinity. Treatment with cortisol allowed us to achieve circulating cortisol levels similar to those observed during osmotic adaptation and to assess how elevated hormonal levels affected simultaneously metabolic and osmoregulatory capacities of the gill tissue. Cortisol-implanted fish showed higher gill Na+,K+-ATPase activity than control fish but no changes were observed in plasma osmolality and ion levels. Plasma levels of glucose and lactate increased in cortisol-implanted fish while protein levels decreased. Cortisol treatment elicited metabolic changes in liver and brain reflecting an activation of the glycogenic and gluconeogenic potential in liver, and the glycogenic potential in brain, which are confirmatory of data obtained in previous experiments. In gills, we demonstrated that cortisol treatment elicited changes in their energy metabolism that can be summarized as a decreased capacity in the use of exogenous glucose (decreased HK activity), a decrease in the capacity of the pentose phosphate pathway (decreased G6PDH activity), and an increased glycolytic potential (increased PK activity). Observed metabolic changes in gills can be associated with those occurring in nature during osmotic adaptation in the same fish species.

Anticipatory changes in liver metabolism and entrainment of insulin, glucagon, and corticosterone in food-restricted rats.

Restricted feeding schedules entrain behavioral and physiological circadian rhythms, which depend on a food-entrainable oscillator (FEO). The mechanism of the FEO might depend on digestive and endocrine processes regulating energy balance. The present study characterizes the dynamics of circulating corticosterone, insulin, and glucagon and regulatory parameters of liver metabolism in rats under restricted feeding schedules. With respect to ad libitum controls, food-restricted rats showed 1) an increase in corticosterone and glucagon and a decrease in insulin before food access, indicating a predominant catabolic state; and 2) a reduction in lactate-to-pyruvate and beta-hydroxybutyrate-to-acetoacetate ratios, indicating an oxidized cytoplasmic and mitochondrial redox state in the liver metabolism. All these changes were reversed after feeding. Moreover, liver energy charge in food-restricted rats did not show a significant modification before feeding, despite an increase in adenine nucleotides, but showed an important decrease after food intake. Variations detected in the liver of food-restricted rats are different from those prevailing under 24-h fasting. These observations suggest "anticipatory activity" of the liver metabolism to optimize the processing of nutrients to daily feeding. Data also suggest a possible relationship of the liver and endocrine signals with the FEO.

Fasciola hepatica infection in sheep: changes in liver metabolism

Several aspects of liver function during infection with Fasciola hepatica were examined in sheep four weeks after infection and compared with the changes observed in infected rats. Previously reported respiratory abnormalities in mitochondria isolated from the left lobe of the liver of infected sheep were characterised further. Evidence is presented that the respiratory lesion is located in the mitochondrial electron transport chain and that the aberrant respiratory behaviour is not associated with an increase in non-esterified fatty acids and the depletion of mitochondrial phospholipids, as is the case in the rat. Microsomal membranes, which have also been shown to be depleted of phospholipids in the fluke-infected rat liver, showed no such changes in the sheep. However, in common with the rat, a substantial loss of cytochrome P 450 was recorded in microsomes prepared from the left lobe, and the glycogen content of the left lobe was found to be less than 50 per cent of control values. No change was observed in glucose 6-phosphatase activity. All these changes were localised effects, confined to areas of fluke infiltration.

Effects of vanadate supplementation on high fat-diet and diabetes-induced metabolic changes in liver

Normal and streptozotocin-induced diabetic rats were fed the control high starch-diet or a high fatdiet supplemented with or without sodium orthovanadate (1.5 mg/g diet) for six weeks. Plasma glucose, insulin and triacylglycerol levels and the activities of hepatic glycogen synthase, phosphorylase, glucose-6-phosphate dehydrogenase, malic enzyme, and ATP-citrate lyase were measured in these eight groups of rats. The high fat-diet increased the levels of insulin (P<0.05) and triacylglycerol (P<0.01) in plasma and decreased the activities (P<0.001) of phosphorylase (active from and total) and the lipogenic enzymes. Vanadate supplementation led to significant (P<0.001) decreases in the elevated insulin and triacylglycerol levels whereas the enzyme activities remained unaffected. Diabetes and fat diet in combination caused 3.7-fold increases in plasma glucose and triacylglycerol levels and vanadate decreased them by 58% and 74% respectively. Vanadate improved the activities of hepatic glycogen metabolizing and lipogenic enzymes in diabetic rats when they were fed on control starch-diet but not with high fat-diet. This study shows that vanadate normalizes hyperinsulinemia and hypertriglyceridemia but not the defective hepatic glycogen metabolism in high fat-fed rats.

Effects of acute alcohol intoxication on gluconeogenesis and its hormonal responsiveness in isolated, perfused rat liver

Rats were acutely administered ethanol as a primed constant infusion in order to produce sustained blood ethanol levels of 8–12 or 55–65 mM. At the end of ethanol infusion the livers were either freeze-clamped in vivo or isolated and perfused for metabolic studies. The rate ofgluconeogenesis and its responsiveness to phenylephrine (10μM), prostaglandin F 2α (5μM) and glucagon (10 nM), as well as the redox state of the cytosolic NAD +-NADH system were assessed in livers isolated from acutely ethanol-treated rats, and subsequently perfused without ethanol. For liver clamped in vivo, high- but not low-ethanol treatment decreased the ATP content by 31% and slightly increased ADP and AMP content, resulting in a decreased energy charge (11%). Glutamate and aspartate content was also increased in high-dose ethanol-infused rats with no changes in malate and 2-oxoglutarate content. Gluconeogenesis with saturating concentrations of lactate (4 mM) + pyruvate (0.4 mM) was delayed in reaching a plateau in the livers of high-dose ethanol-treated rats and its response to all three stimulators was impaired. Low-dose ethanol treatment only decreased the liver response to phenylephrine. While the perfused livers of low-dose ethanol-treated rats displayed no changes in adenine nucleotide content, the livers of high-dose ethanol-treated rats had a decreased ATP (35%) and an increased AMP (77%) content, paralleled by a fall in the total adenine nucleotides (14%) and energy charge (14%). No differences were observed between the saline- and ethanol-treated rats with respect to malate-aspartate shuttle intermediate concentration in perfused livers. Also, the livers of high-, but not low-dose ethanol-treated rats had a more negative value of NAD +-NADH redox state as compared to the livers of control rats. The data suggest that acute ethanol intoxication produces changes in liver metabolism and its responsiveness to hormones/agonists that are demonstrable for at least 2 hr after isolation and perfusion of the liver.

Effect of hypothyroidism on phosphorus metabolism in muscle and liver: in vivo P-31 MR spectroscopy study.

Hypothyroidism is known to affect nearly every organ and organ system of the human body. The goal of the present study was to gain insight into the phosphorus metabolism and bioenergetic function of striated (calf) muscle and liver in patients with hypothyroidism before and after thyroid hormone treatment. With an ISIS (image-selected in vivo spectroscopy) magnetic resonance (MR) technique for volume selection, phosphorus-31 metabolism of the calf muscle in 10 patients and of the liver in seven patients with severe hypothyroidism was studied before and after treatment. In addition, spectra from the calf muscle and liver were obtained in 10 healthy volunteers. Relative to those from the healthy subjects, the P-31 MR spectra from patients with hypothyroidism showed a significantly diminished phosphocreatine/inorganic phosphate ratio (P less than .01). After thyroid hormone substitution therapy, this ratio returned to normal values within several weeks. No statistically significant changes in the spectra of liver tissue could be detected. The results support the theory that hypothyroidism induces a hormone-dependent, fully reversible impairment of the energy metabolism of striated muscle. Changes in liver metabolism observed with biochemical methods are apparently not detectable with state-of-the-art P-31 MR spectroscopy.

Effects of Long-Acting Superoxide Dismutase on Liver Metabolism after Major Hepatic Resection in Rats with Cirrhosis

The aim of this study is to clarify the liver metabolic changes after major hepatic resection. The survival rate after 70% hepatectomy of rats with cirrhosis was significantly depressed compared with that of the control group. Mitochondrial function in the cirrhotic liver was disturbed compared with the control group. Tissue levels of hypoxanthine and xanthine increased both in the cirrhotic group and the control group. The increase in xanthine levels was remarkable and was prolonged in the cirrhotic group compared with the control group. Decreases in adenine nucleotides were observed after resection both in normal and cirrhotic livers. These were remarkable and were prolonged in rats with cirrhosis. Administration of polyoxyethylene-modified superoxide dismutase improved the survival rate and lessened decreases in adenine nucleotide levels. Moreover, it accelerated the recoveries of serum glutamic oxaloacetic and pyruvic transaminase levels after resection in rats with cirrhosis. These results indicate that disturbances in energy metabolism and increases in oxygen free radical formation are more remarkable in the cirrhotic liver than in the normal liver, which contributes to a low survival rate in rats with cirrhosis.

Dexamethasone increases glucose cycling, but not glucose production, in healthy subjects

We established that measurement of glucose fluxes through glucose-6-phosphatase (G-6-Pase; hepatic total glucose output, HTGO), glucose cycling (GC), and glucose production (HGP), reveals early diabetogenic changes in liver metabolism. To elucidate the mechanism of the diabetogenic effect of glucocorticoids, we treated eight healthy subjects with oral dexamethasone (DEX; 15 mg over 48 h) and measured HTGO with [2-3H]glucose and HGP with [6-3H]glucose postabsorptively and during a 2-h glucose infusion (11.1 mumol.kg-1.min-1). [2-3H]- minus [6-3H]glucose equals GC. DEX significantly increased plasma glucose, insulin, C peptide, and HTGO, while HGP was unchanged. In controls and DEX, glucose infusion suppressed HTGO (82 vs. 78%) and HGP (87 vs. 91%). DEX increased GC postabsorptively (three-fold) P less than 0.005 and during glucose infusion (P less than 0.05) but decreased metabolic clearance and glucose uptake (Rd), which eventually normalized, however. Because DEX increased HTGO (G-6-Pase) and not HGP (glycogenolysis + gluconeogenesis), we assume that DEX increases HTGO and GC in humans by activating G-6-Pase directly, rather than by expanding the glucose 6-phosphate pool. Hyperglycemia caused by peripheral effects of DEX can also contribute to an increase in GC by activating glucokinase. Therefore, measurement of glucose fluxes through G-6-Pase and GC revealed significant early effects of DEX on hepatic glucose metabolism, which are not yet reflected in HGP.

The effect of avocado oils on some liver characteristics in growing rats

The effects of various avocado oils on some liver characteristics were studied in growing rats. The rats were fed diets containing 10% (w/w) avocado oil for 4 wk. In comparison with rats fed refined oil obtained from cored fruit by centrifugal separation, rats fed unrefined avocado oil obtained by solvent extraction from the intact fruit, or refined avocado oil containing avocado-seed oil, showed significant growth inhibition, an increase in the amount of hepatic lipids (identified as steatosis by histopathological examination), and a decrease in levels of triglycerides in blood. Rats fed the refined oil containing unsaponifiable material prepared from unrefined oil from the intact fruit showed similar responses. Fatty livers were not induced by feeding rats unrefined avocado oil obtained from intact fruit by centrifugal separation, although a significant decrease in blood triglycerides was observed. There were no significant differences between groups in serum total protein, albumin or bilirubin content or in alanine aminotransferase activity. However, serum alkaline phosphatase activity was increased in rats fed the seed oil, the unrefined solvent-extracted oil from intact fruit, or the unsaponifiables, and aspartate aminotransferase activity was significantly increased in the group fed avocado-seed oil. These data suggest that consumption of avocado oil extracted from intact fruit may cause changes in liver metabolism.

Influences of nifedipine on vascular conductance of portally drained viscera, liver and kidney

Nifedipine is a potent vasodilator, which induces various dose-related hemodynamic responses in the gastrointestinal tract, liver and kidney. Blood flow was assessed in anesthetized dogs with non-cannulating electromagnetic flow sensors. Nifedipine was injected into a brachial vein at intervals of 2 min in graded doses from 1–16 μg · kg −1. The pulsatile flow and pressure signals were analog-digital converted and processed by a computer program to obtain mean flow (ml · min −1) and mean pressure (mm Hg) values for every 3 s. The vascular data are presented as conductance. The arterial pressure decreased 45% while vascular conductance in vessels of the stomach, duodenum, small and large bowel increased between 75 and 128%. No response was observed in the splenic and common hepatic artery. An increase of resistance in the hepatic artery proper, while portal flow increased suggests that there were changes in liver metabolism. Although the literature indicates a decrease in renal vascular resistance, we encountered a decrease in flow but no change in resistance. Neither did we find an increase in heart rate. We propose that small intravenous doses of nifedipine reduce the afterload of the left ventricle.

Liver metabolic effects of intestinal shock and naloxone treatment in the rat.

The liver metabolic response of rats following a standardized intestinal shock, induced by applying a pressure of 120 cm water on the mesenteric vessels for 60 min, was studied. Immediately prior to the release of the pressure on the vessels saline or naloxone was given either as a single injection or as a continuous infusion. After the reperfusion of the intestine no early disturbances in liver metabolism were found as evidenced from the ATP, glucose and lactate levels in liver biopsies taken 15 min following reflow. Within 60 min of reflow reduction of ATP and increases of glucose and lactate levels occurred. There were no major hemodynamic or liver metabolic differences between saline- and naloxone-treated shocked rats. When saline or naloxone was given as a continuous infusion, the changes in liver metabolism were, however, less severe than those observed in the single injection situation pointing toward a non-specific effect of volume replacement rather than a blockade of opioid receptors. Hepatic hypoxia and/or cellular effects of "shock factors" could be mechanisms of pathophysiologic importance for the disturbed liver metabolism in this shock model.

Enzymatic Changes in Pancreas and Liver of the KK Mouse As an Animal Model of Diabetes Mellitus

KK mice are used as model animals for non-insulin-dependent diabetes. In order to better understand the biochemical features of these animals, we compared the activities of various hydrolytic enzymes, including aminopeptidases, endopeptidases, carboxypeptidase, esterase, and so forth in the pancreas and liver of these animals with the same enzymes in ICR mice as controls. The enzymatic changes in the model animals were extensive not only in pancreas but also in liver. Multivariate analysis showed that the metabolic changes in liver rather than in pancreas are closely related to the abnormal glucose metabolism in KK mice. This may be somehow related to the insulin resistance in peripheral tissues in this model.

Hepatic control of food intake

Russek's (1981 a) review of the "hepatostatic" theory states that food absorbed from the intestine causes a change in liver metabolism that in turn affects food intake. The results of two of my experiments are in conflict with the theory. In one experiment, food absorbed in physiological amounts from the intestine of the rat failed to cause a decrease in subsequent food intake. In the other experiment, food absorbed from the intestine was diverted into the systemic blood through the use of a portacaval shunt. In spite of a decrease in the amount of absorbed food that would flow to the liver, there was no increase in food intake. These experiments fail to support the "hepatostatic theory".

Correction of metabolic changes in liver of tumor-bearing mice following curative resection

The hepatic contents of free coenzyme A, acetyl CoA, citrate, and α-oxoglutarate were determined in mice bearing a subcutaneous transplantable C 3H mammary tumor which remained localized. The free CoA and acetyl CoA content of these livers showed significant decreases. A curative resection reverted these changes to normal, but where the resection was unsuccessful, changes in the hepatic content of these metabolites again occurred. Mean spleen weights in animals bearing the tumor were significantly increased, but returned to normal following curative resection. Mean thymus weights did not alter in mice bearing the tumor when the mean weight was 0.55 ± 0.11 (SEM) g, but a sham operation on normal mice induced thymic atrophy, and significant decreases in the hepatic content of citrate. It is suggested that changes in the hepatic contents of free CoA and acetyl CoA in mice bearing this tumor are induced by some product of tumor origin.

Metabolic changes in liver of tumor-bearing mice

The hepatic contents of acetyl coenzyme A, free CoA, α-oxoglutarate, and citrate were determined in tumor-bearing mice. Significant decreases in acetyl CoA and free CoA, with a concomitant increase in citrate occurred 24 hr following inoculation of TLX-5 lymphoma cells. Similar changes occurred in mice bearing a C 3H mammary tumor, when the latter was just palpable in situ. There was some indication that in mice bearing Sarcoma 180, the size of the tumor was a factor in inducing these changes. Significant decreases in the α-oxoglutarate content of liver could only be detected in mice bearing the lymphoma or Sarcoma 180. The direction of change in the hepatic contents of acetyl CoA and citrate were opposite to those found in tumor-free animals under gluconeogenic conditions. However, significant increases in citrate would favor gluconeogenesis by inhibition of phosphofructokinase. Starvation of tumor-bearing mice failed to increase the acetyl CoA content of liver or decrease citrate. The data suggest a failure in lipolysis, as well as in the regulation of fatty acid synthesis in liver via changes in citrate.

Influence of nutritional state on periodicity in plasma insulin levels in monkeys.

Rapid sustained oscillations in basal plasma levels of insulin, glucose, and glucagon (9-12 min/cycle) have been identified in rhesus monkeys and in humans. To assess the possible regulatory role of nutritional state in the control of these plasma fluctuations, 12 chronically cannulated conscious rhesus monkeys were studied at varying intervals following ingestion of a mixed meal. Blood samples were withdrawn at 2-min intervals for periods of 10-30 min. In the postprandial period both absolute and relative amplitudes (half amplitude percent) of oscillations increased up to 16 h postfeeding to maximal amplitudes of +/- 32% for insulin, +/- 4% for glucose, and +/- 22% for glucagon. Periods were consistently in the 9- to 12-min range for insulin and glucose. Progressive deprivation to 88 h produced decreases in amplitudes and more irregularity in fluctuations but did not affect the underlying periodicity of these oscillations in plasma levels of insulin, glucose, and glucagon. Results are consistent with the existence of one or more inherent oscillators in the pancreas that act to synchronize the release of hormones from particular types of islet cells. The amplitude of these oscillations but not the frequencies is associated with changes in liver metabolism and nutritional state.

The effect of glucagon, dibutyrylic cyclic AMP and theophylline on bile production in the cat

The effect of glucagon, dibutyrylic cyclic AMP and theophylline on bile production and liver metabolism was studied in fasting, chloralose anesthetized cats. After 45 min infusion of glucagon (0.1 mug/kg/min) total bile flow started to increase and finally reached a level 32% above control bile flow. The rise in flow was accompanied by a parallel increase in the biliary clearance of erythritol and the rate of biliary excretion of inorganic ions, whereas the bile acid excretion remained constant. Glucagon therefore appears to stimulate selectively the bile acid-independent canalicular production of bile. In contrast to the delayed action on bile production, glucagon caused an immediate change in liver metabolism as judged from the elimination rate of ethanol and the rise in plasma glucose concentration. Dibutyrylic cyclic AMP or theorphylline also caused similar immediate changes in liver metabolism but neither substance influenced bile production or the biliary excretion of electrolytes or bile acids. It thus appears that glucagon choleresis in the cat is either independent of cAMP release or that an increase in intracellular cAMP is not in itself sufficient to influence bile secretion. The results also seem to exclude that an increase in insulin production induced by hyperglycemia, or hemodynamic changes in the liver, can explain glucagon choleresis.

Alteration of plasma lipids and intermediates of lipid metabolism in healthy fasting volunteers by ethanol and fructose

After healthy persons, aged between 20 and 35 years, had consumed either ethanol or ethanol and fructose, triglycerides, free glycerol, FFA, phospholipids and total cholesterol were determined. After a basic dosage of 0.5 g ethanol/kg body weight, each person received a maeintenance dosage of 0.1 g ethanol/kg body weight and hour. Control experiments were carried out on persons receiving only fructose and on fasting persons who consumed no ethanol. After 8 hrs, triglycerides rose in the ethanol group by 107 %, in the ethanol-fructose group by 63 %. FFA exhibited in both ethanol and ethanol-fructose groups an initial decrease, with a secondary increase in the ethanol group. The initial decrease was greater in the ethanol-fructose group. A significant rise in free glycerol by 419 % was observed 30 min after the intake of combined ethanol/fructose. Free glycerol rose under ethanol alone by 144%. The ohospholipids exhibited a slight rise in the ethanol group; no significant changes occured in the cholesterol. The blood ethanol level was lower under ethanol-fructose than under ethanol alone. The addition of fructose diminishes the ethanol-induced hypertriglyceridemia. Our investigations give further proof that, under short-term ethanol load, the fatty acids necessary for the increased triglyceride synthesis in the liver, originate predominantly from a peripheral lipolysis, and that changes in liver metabolism depending on the oxidation of ethanol are not of less importance for the development of the acute ethanol-induced hyperlipidemia.