Consumption Of Free Fatty Acids Research Articles

Abstract 15407: Benefits of the Sglt2 Inhibitor Empagliflozin on Epicardial Adipose Tissue in Non-Diabetic Hfref

Introduction: SGLT2 inhibitors cause weight loss, and reduce epicardial adipose tissue (EAT) on T2DM. The effects of T2DM on non-diabetic HFrEF remain unclear. Methods: HFrEF was induced in non-diabetic pigs via percutaneous oclusion of LAD (LVEF 30±4%). Animals were randomized to empagliflozin 10mg daily or placebo (n=8/group) for 2 months, and animals were subsequently euthanized. Cardiac MRI and echocardiography were performed before and after treatment. Invasive hemodynamics, histology and molecular biology were performed at 2-months. Primary culture of adipocytes from EAT was performed. Results: Empagliflozin caused reverse LV remodeling, reduced LVEDV and improved LVEF (Table). EAT volume was inversely associated with myocardial consumption of free fatty acids (r=-0.6, p=<0.05). Empagliflozin reduced EAT, both as MRI-determined EAT volume and histologically-evaluated adipocyte size (Table). Empagliflozin induced lipolysis in the adipocytes from EAT, as demonstrated by lower levels of triglycerides and perilipin (main protein responsible for triglyceride storage), and higher levels of the lipolytic enzymes lipoprotein lipase and hormone-sensitive lipase. Empagliflozin caused an anti-inflammatory effect on EAT as shown by lower levels of macrophage infiltration and MCP-1. Empagliflozin exerted antioxidant actions, as per reduced levels of 8-OH-deoxyguanosine and malonildealdehide (oxidative stress markers in nuclei and protein, respectively. Conclusions: Empagliflozin exerts multiple benefits on EAT in non-diabetic HFrEF. Empagliflozin induces a lipolytic state that reduces EAT volume, and it also ameliorates the oxidative and inflammatory status of EAT.

High temperature corrosion in various grades of vegetable and waste oils used for bio-fuel production

Corrosion experiments were conducted at 220 °C in vegetable and waste oils used to produce biofuels. Industrial oils and model solutions with controlled concentrations of free fatty acids (FFA) were used. Corrosion of carbon steel and low alloy steel increased with FFA concentration up to several millimeters per year. AISI 316 L stainless steel was immune to corrosion in all FFA concentrations used in this study. Test solution analysis with various techniques allowed identifying corrosion mechanisms involving consumption of FFAs and the formation of highly soluble metal complexes.

Overexpression of CD36, Driven By STAT3, Mediates Free Fatty Acid Uptake in CLL Cells

Overexpression of CD36, Driven By STAT3, Mediates Free Fatty Acid Uptake in CLL Cells

Moringa oleifera leaf extract influences oxidative metabolism in C2C12 myotubes through SIRT1-PPARα pathway

BackgroundMoringa oleifera is an important traditional multipurpose plant, due to the presence of many bioactive compounds. Moringa oleifera leaf extracts (MOLE) have been shown to have many beneficial properties in pathological conditions including diabete. However, the lack of information about its exact molecular mechanism of action might hinder other potential use in different areas such as skeletal muscle physiology. Hypothesis/purposeSkeletal muscle represents about 40-50% of the total mass of a lean individual and is an insulin-sensitive tissue with wide variations in energy requirements. We aimed to test the effects of MOLE on oxidative metabolism and the molecular mechanism involved on myotubes by using C2C12 cell line, a well known model for in vitro skeletal muscle studies. Study designC2C12 myotubes were treated with MOLE at different working solutions for 24 and 48 hours and then culture media and cellular extracts were collected. MOLE was screened for phytochemicals determination. MethodsGlucose and free fatty acids consumption along with lactate release were assessed in the culture media. Citrate sinthase, 3-hydroxy acylCoA dehydrogenase, alanine transglutaminase and creatine kinase enzyme activities, as well as the metabolic regulatory SIRT1 and PPARα protein levels were evaluated in cellular extracts. ResultsMOLE administration induced a dose and time dependent increase in substrates consumption accompanied by an increase in intracellular oxidative metabolism enzymatic activity levels. The extracts were also able to modulate positively the protein expression of SIRT1 and PPARα. ConclusionAltogether, these data indicate that MOLE could represent a valid nutritional support for improving skeletal muscle metabolism: in fact MOLE treatment increased oxidative energy metabolism and possibly favours mitochondrial biogenesis through SIRT1/PPARα pathway. future studies will clarify wether Moringa oleifera leaf extracts consumption may be useful to improve physical performance and metabolic-related skeletal muscle diseases.

Chronic Urotensin-II Administration Improves Whole-Body Glucose Tolerance in High-Fat Diet-Fed Mice.

Urotensin-II (U-II) is an endogenous peptide agonist of a G protein-coupled receptor—urotensin receptor. There are many conflicting findings about the effects of U-II on blood glucose. This study aims to explore the effects of U-II on glucose metabolism in high-fat diet-fed mice. Male C57BL/6J mice were fed a 45% high-fat diet or chow diet and were administered U-II intraperitoneally for in vivo study. Skeletal muscle C2C12 cells were used to determine the effects of U-II on glucose and fatty acid metabolism as well as mitochondrial respiratory function. In this study, we found that chronic U-II administration (more than 7 days) ameliorated glucose tolerance in high-fat diet-fed mice. In addition, chronic U-II administration reduced the weight gain and the adipose tissue weight, including visceral, subcutaneous, and brown adipose tissue, without a significant change in blood lipid levels. These were accompanied by the increased mRNA expression of the mitochondrial thermogenesis gene Ucp3 in skeletal muscle. Furthermore, in vitro treatment with U-II directly enhanced glucose and free fatty acid consumption in C2C12 cells with increased aerobic respiration. Taken together, chronic U-II stimulation leads to improvement on glucose tolerance in high-fat diet-fed mice and this effect maybe closely related to the reduction in adipose tissue weights and enhancement on energy substrate utilization in skeletal muscle.

IDO decreases glycolysis and glutaminolysis by activating GCN2K, while it increases fatty acid oxidation by activating AhR, thus preserving CD4+ T‑cell survival and proliferation.

It is generally hypothesized in the literature that indoleamine 2,3‑dioxygenase (IDO), by degrading L‑tryptophan along the kynurenine pathway, suppresses CD4+ T‑cell function by inducing apoptosis, inhibiting proliferation and promoting differentiation towards a regulatory phenotype. These effects are either accompanied or directly lead to alterations in cell metabolism. The present study evaluated the pathways that govern the effect of IDO on the utilization of the three main energy sources in CD4+T‑cells. Two‑way mixed lymphocyte reactions were performed with or without oleate and/or the IDO inhibitor 1‑methyl‑DL‑tryptophan. In addition, isolated CD4+T‑cells cultured in an oleate‑containing medium were activated in the presence or not of the general control nonderepressible2 kinase (GCN2K) activator tryptophanol. L‑tryptophan, glucose and free fatty acid consumption, cell proliferation, apoptosis and the levels of key proteins involved in IDO‑mediated signal transduction, and glucose, glutamine and free fatty acid utilization were assessed. The results indicate that IDO decreased glycolysis and glutaminolysis by activating GCN2K, resulting in activation of AMP‑activated protein kinase (AMPK). In parallel with AMPK activation, IDO‑induced activation of aryl hydrocarbon receptor increased the expression of all carnitine palmitoyltransferase I isoenzymes, leading ultimately to increased free fatty acid oxidation and preservation of CD4+ T‑cell survival and proliferation. Thus, contrary to what is generally hypothesized, in a normal environment containing fatty acids, the immunosuppressive effect of IDO may not be due to a decrease in CD4+ T‑cell survival and proliferation, since IDO supplies the required energy for cell survival and proliferation by increasing free fatty acid oxidation.

Three-dimensional perfused human in vitro model of non-alcoholic fatty liver disease.

AIMTo develop a human in vitro model of non-alcoholic fatty liver disease (NAFLD), utilising primary hepatocytes cultured in a three-dimensional (3D) perfused platform.METHODSFat and lean culture media were developed to directly investigate the effects of fat loading on primary hepatocytes cultured in a 3D perfused culture system. Oil Red O staining was used to measure fat loading in the hepatocytes and the consumption of free fatty acids (FFA) from culture medium was monitored. Hepatic functions, gene expression profiles and adipokine release were compared for cells cultured in fat and lean conditions. To determine if fat loading in the system could be modulated hepatocytes were treated with known anti-steatotic compounds.RESULTSHepatocytes cultured in fat medium were found to accumulate three times more fat than lean cells and fat uptake was continuous over a 14-d culture. Fat loading of hepatocytes did not cause any hepatotoxicity and significantly increased albumin production. Numerous adipokines were expressed by fatty cells and genes associated with NAFLD and liver disease were upregulated including: Insulin-like growth factor-binding protein 1, fatty acid-binding protein 3 and CYP7A1. The metabolic activity of hepatocytes cultured in fatty conditions was found to be impaired and the activities of CYP3A4 and CYP2C9 were significantly reduced, similar to observations made in NAFLD patients. The utility of the model for drug screening was demonstrated by measuring the effects of known anti-steatotic compounds. Hepatocytes, cultured under fatty conditions and treated with metformin, had a reduced cellular fat content compared to untreated controls and consumed less FFA from cell culture medium.CONCLUSIONThe 3D in vitro NAFLD model recapitulates many features of clinical NAFLD and is an ideal tool for analysing the efficacy of anti-steatotic compounds.

Influence of vacuum on kinetic of low quality rapeseed oil amidation by aminoethylethanolamine

The process of direct amidation of low­grade canola oil with high free fatty acids content has been researched. Influence of different technological parameters on consumption of reagents and accumulation of reaction products have been established for the temperature of reaction 160 °С. Concentrations of esters, free fatty acids, alkylimidazolines and amine components have been determined during the reaction time. Application of vacuum during the amidation process has great influence on free fatty acids consumption as well as on alkylimidazoline formation. Effective rate constants have been calculated for reactions of conversion of free fatty acids and esters into amides with and without vacuum. It has been determined that effective rate constant of free fatty acids consumption under atmospheric pressure is three times lower than under vacuum 40–60 mm. Hg. as well as those for esters. Along with an increase in free fatty acids consumption, the speed of alkylimidazolines formation rapidly increases with vacuum applying. Such effect is explained by shifting of equilibrium in reactions of free fatty acids consumption and alkylimidazoline formation by removing of reaction water by vacuum. Formation of amides of fatty acids and alkylimidazolines confirmed by IR­spectroscopy.

Production of esters from soybean oil deodorizer distillate in pressurized ethanol

The aim of this study was to obtain esters from soybean oil deodorizer distillate (SODD) in pressurized ethanol without the use of a catalyst. Experiments were carried out to evaluate the effects of the operating variables (pressure, temperature, residence time and ethanol to free fatty acids molar ratio) using a minimum factorial experimental design. The results indicate that increasing the temperature, pressure and residence time in the reactor enhanced the conversion of free fatty acids (FFA) while increasing the ethanol to FFA molar ratio decreased the conversion. The experiment carried out under optimum conditions (20MPa, 275°C, 20min and ethanol to FFA molar ratio of 7:1) reached ~87% of FFA conversion. The reaction kinetics was investigated at different temperatures and the results obtained reveal that a high rate of FFA consumption and conversions close to the thermodynamic equilibrium were quickly reached. At high temperatures (325 and 350°C) the conversion decreased with increasing residence time, indicating that the reverse reaction occurred. The reaction in two steps increased the FFA conversion, indicating that the conversions obtained were close to the thermodynamic equilibrium and the removal of water between the steps shifted the equilibrium, making it possible to achieve higher FFA conversion and ester yields.

Bioconversion of mixed free fatty acids to poly-3-hydroxyalkanoates by Pseudomonas putida BET001 and modeling of its fermentation in shake flasks

Background: The paper reports on the utilization of palm kernel oil (PKO) as a low cost renewable substrate for medium-chain-length poly-3-hydroxyalkanoates (mcl-PHA) production by Pseudomonas putida BET001. Investigation on the effects of selected key variables on growth, mixed free fatty acids consumption and mcl-PHA production by the bacterial culture in the shaken flask system were carried out along with its kinetic modeling. Results: The biomass production, fatty acids consumption and mcl-PHA production were found favorable when the strain was cultured in mineral medium at pH 6-7, 28°C, aeration surface-to-volume ratio of 0.4 × 10 6 m - 1 , 250 rpm agitation rate for 48 h. Mcl-PHA production by this strain showed mixed growth and non-growth associated components as described by Luedeking-Piret kinetic model. Conclusion: The findings of this study provided add to the literature on key variables in for achieving good microbial growth and mcl-PHA production in shake flasks culture. In addition, suitable kinetic model to describe cultivation in this system was also presented. Normal 0 21 false false false ES-CL X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:Tabla normal; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:Calibri,sans-serif; mso-ansi-language:ES-CL; mso-fareast-language:ES-CL;}

A PET-Compatible Tissue Bioreactor for Research, Discovery, and Validation of Imaging Biomarkers and Radiopharmaceuticals: System Design and Proof-of-Concept Studies

Research and discovery of novel radiopharmaceuticals and targets thereof generally involves initial studies in cell cultures, followed by animal studies, both of which present several inherent limitations. The objective of this work was to develop a tissue bioreactor (TBR) enabling modulation of the microenvironment and to integrate the TBR with a small-animal PET scanner to facilitate imaging biomarker research and discovery and validation of radiopharmaceuticals. The TBR chamber is a custom-blown, water-jacketed, glass vessel enclosed in a circulating perfusion bath powered by a peristaltic pump, which is integrated within the field of view of the PET scanner. The chamber is in series with a gas exchanger and a vessel for degassing the system during filling. Dissolved oxygen/temperature probes and septa for injection or sampling are located at the inlet and outlet of the cell chamber. A pH probe is located at the chamber outlet. Effluent is collected in the fraction collector as mixed-cup samples. In addition, both medium and tissue chamber can be sampled to investigate tissue and secretory products through multiscale analysis. As a proof of concept, we studied the effects of lipids on glucose uptake using HepG2 cells. To that end, we varied the nutrient substrate environment over a period of approximately 27 d, before and after the addition of lipids, and studied the effects of pioglitazone, a peroxisome proliferator-activated receptor γ agonist, on lipid and glucose uptake. In parallel, the TBR was imaged by PET in conjunction with (11)C-palmitate in the presence and absence of lipids to characterize (11)C-palmitate uptake. The O2 consumption, glucose consumption, lactate production, and free fatty acid consumption and production rates were consistent in demonstrating the effects of lipids on glucose uptake. Pioglitazone exhibited improved glucose uptake within 3 d of treatment. Semiquantitative analysis suggested that lipids induced greater (11)C-palmitate uptake. The integrated TBR offers a platform to monitor and modulate the tissue microenvironment, thus facilitating tissue-specific imaging and therapeutic biomarkers of disease, identification of molecular diagnostic markers, and validation of radiopharmaceuticals in both rodent and human cell lines.

Role of nitric oxide in the regulation of substrate metabolism in heart failure.

Solid experimental evidence indicates that nitric oxide (NO) inhibits oxygen utilization in vitro and in vivo. The role played by NO in cellular metabolism is likely extended to the control of substrate utilization. Studies performed in normal hearts show that NO inhibits glucose uptake and that a reduced synthesis of NO impairs free fatty acid consumption. Interestingly, we found also that myocardial free fatty acid utilization decreases while glucose consumption is enhanced in end stage heart failure, when cardiac NO production falls dramatically. This phenomenon led us to the hypothesis that the reduced synthesis of NO could be at least in part responsible for myocardial metabolic alterations occurring in severe heart failure. The present review mentions some of the seminal studies that defined the function of NO as metabolic modulator. A particular emphasis is put on available data suggesting a role for NO in the control of cardiac substrate utilization in normal and failing hearts.

Bovine polymerized hemoglobin increases cardiac oxygen consumption and alters myocardial substrate metabolism in conscious dogs: role of nitric oxide.

We investigated the effect of bovine polymerized hemoglobin-based oxygen carrying (HBOC) solution on myocardial oxygen consumption (MVO2) and substrate use. At 15 min after the end of HBOC infusion (20% blood volume, i.v.) in nine permanently instrumented conscious dogs, mean arterial pressure and coronary blood flow were both increased by 41+/-5% and 93+/-20% (p<0.01) without affecting late diastolic coronary resistance and left ventricular dP/dtmax. Administration of HBOC did not affect arterial PO2 or O2 content, but significantly decreased coronary sinus PO2 and O2 content by 21+/-3% and 36+/-3%, respectively. MVO2 was increased from 7.2+/-0.8 to 15+/-1.8 ml O2/min (p<0.01). Despite an increase in triple product from 44+/-2 to 56+/-3 (p<0.01) 15 min after HBOC, the ratio of MVO2 and triple product was markedly elevated by 62+/-19%. Myocardial free fatty acid consumption was decreased from 14+/-1 to 4.5+/-2.2 microEq/min, whereas consumption of lactate increased from 19+/-6 to 69+/-10 micromol/ min and that of glucose increased from 1.0+/-0.5 to 10+/-3 mg/min (all p values, <0.05). These metabolic changes were not observed in dogs that received angiotensin II at a dose used (20-40 ng/kg/min, i.v.) to match those hemodynamic effects of HBOC. These results suggest that administration of HBOC increases coronary blood flow and MVO2 and shifts cardiac metabolism from using free fatty acid to using lactate and glucose in conscious dogs at rest. These metabolic changes are independent of the HBOC-induced change in hemodynamics.

Function and production of nitric oxide in the coronary circulation of the conscious dog during exercise.

This study determined the changes in NO production from the coronary circulation of the conscious dog during exercise. The role of endogenous NO as it relates to coronary flow, myocardial work, and metabolism was also studied. Mongrel dogs were chronically instrumented for measurements of coronary blood flow (CBF), ventricular and aortic pressure, and ventricular diameter, with catheters in the aorta and coronary sinus. Acute exercise (5 minutes at 3.6, 5.9, and 9.1 mph) was performed, and hemodynamic measurements and blood samples were taken at each exercise level. Nitro-L-arginine (NLA, 35 mg/kg IV) was given to block NO synthesis, and the exercise was repeated. Blood samples were analyzed for oxygen, plasma nitrate/nitrite (an index of NO), lactate, glucose, and free fatty acid (FFA) levels. Acute exercise caused significant elevations in NO production by the coronary circulation (46 +/- 23, 129 +/- 44, and 63 +/- 32 nmol/min at each speed respectively, P < .05). After NLA, there was no measurable NO production at rest or during exercise. Blockade of NO synthesis resulted in elevations in myocardial oxygen consumption and reductions in myocardial FFA consumption for comparable levels of CBF and cardiac work. The metabolic changes after NLA occurred in the absence of alterations in myocardial lactate or glucose consumptions. NO production by the coronary circulation is increased with exercise and blocked by NLA. The absence of NO in the coronary circulation during exercise does not affect levels of CBF, because it shifts the relationship between cardiac work and myocardial oxygen consumption, suggesting that endogenous NO modulates myocardial metabolism.

The effect of temperature on the degradation of triglycerides by a pseudomonad isolated from milk: free fatty acid accumulation as a balance between rates of triglyceride hydrolysis and fatty acid consumption

The lipolysis of triglyceride by a lipolytic pseudomonad, LS107d2, and the net levels of free fatty acids (FFA) in milk cultures of LS107d2 have been studied as a function of temperature. The metabolism of triolein results in the accumulation of oleic acid at 4°C but, at higher temperatures, triolein is hydrolysed without detectable oleate accumulation. Temperature also has a profound effect on the levels of FFA in whole milk cultures of LS107d2, and on the temporal pattern of changes in FFA levels. The results are consistent in demonstrating that FFA consumption plays a significant role in determining the net level of FFA in milk, even in the presence of very high rates of lipolysis. Thus the net levels of FFA as a result of the growth of LS107d2 in milk are the result of a dynamic balance between rates of FFA production (by lipolysis) and subsequent consumption. Temperature can dramatically affect the levels of FFA in milk cultures, and these changes are proposed to be due to opposing influences on FFA consumption and production, affecting the balance between them.

Effects of coronary perfusion during myocardial hypoxia: Comparison of metabolic and hemodynamic events with global ischemia and hypoxemia

The effects of metabolic accumulation on myocardial metabolism during global heart oxygen deprivation were evaluated in a working in situ swine heart preparation with controlled total coronary blood flow. Myocardial oxygen consumption was depressed to a similar extent by either reducing total coronary flow 60 per cent (ischemia, low coronary perfusion) in 10 swine or by decreasing coronary perfusate PO2 to 30 mm. Hg at normal flows (hypoxemia, high coronary perfusion) in 13 swine. Compared with findings in 13 control hearts, ischemia significantly (p less than 0.05) decreased myocardial oxygen consumption (640 to 390 mumole per hour per gram), glucose uptake (185 to 16 mumole per hour per gram), and free fatty acid consumption (32 to 17 mumole per hour per gram). ttissue levels of glycogen, creatine phosphate, and adenosine triphosphate (tatp) were significantly reduced (p less than 0.005), and tissue lactate, adenosine diphosphate (ADP), and adenosine monophosphate (AMP) were increased (p less than 0.001). During hypoxemia, glucose uptake was increased (240 mumole per hour per gram) and free fatty acid consumption was somewhat less depressed (19 mumole per hour per gram). Creatine phosphate and ATP were higher than with ischemia (p less than 0.01), and lactate, ADP, and AMP accumulations were less (p less than 0.01). Thus, in the period immediately following myocardial oxygen deprivation, inadequate coronary perfusion caused greater metabolic buildup which inhibited myocardial substrate utilization and energy production. High coronary perfusion, even though the perfusate was unoxygenated, was associated with greater preservation of substrate utilization, higher levels of high-energy phosphates, less accumulation of metabolic products, and a longer survival. These data suggest a critical role of coronary perfusion in protecting myocardial metabolism in the immediate period following global heart hypoxia.

Myocardial metabolism and performance during sodium salicylate infusion in dogs.

The effect of sodium salicylate on net myocardial free fatty acid (FFA) uptake, myocardial oxygen consumption (MVO2), and the mechanical activity of the heart was studied in eight intact, anesthetized dogs. Sodium salicylate was given intravenously under basal conditions and during isoproterenol-stimulated lipolysis. Under basal conditions, sodium salicylate significantly reduced arterial FFA concentration, but did not influence net myocardial uptake of FFA, and MVO2 was unchanged. During isoproterenol infusion sodium salicylate reduced arterial FFA concentration 28% (P less than 0.01) and significantly reduced net myocardial uptake of FFA from 44.5 +/- 9.0 (mean +/- S.E.M.) to 22.3 +/- 2.1 mumol/min-100g tissue (P less than 0.05) and MVO2 from 20.3 +/- 2.2 to 160 +/- 1.9 ml/min-100g tissue (P less than 0.05). The reduction in MVO2 could not be explained by reduced mechanical activity of the heart. Most probably the mechanism for the reduction in MVO2 effected by sodium salicylate during isoproterenol infusion was mediated by reduced myocardial FFA consumption.

Effects of nicotine and inhalation of cigarette smoke on total body oxygen consumption in dogs.

The effects on total body oxygen consumption of nicotine infused intravenously and of simulated cigarette smoking were studied in intact anesthetized dogs. Nicotine infusion and simulated cigarette smoking raised total body oxygen consumption by 9 plus or minus 2% (mean plus or minus S.E.M.; P smaller than 0.02) and 6 plus or minus 2% (P smaller than 0.05), respectively, and arterial concentration of free fatty acids (FFA) by 29 plus or minus 9% (P smaller than 0.05) and 12 plus or minus 3% (P smaller than 0.01). When nicotine infusion and simulated cigarette smoking were repeated during inhibition of lipolysis with beta-pyridylcarbinol, no rise in total body oxygen consumption occurred, although the mean aortic blood pressure and heart rate remained elevated to levels similar to those during intact lipolysis. It is concluded that the rise in total body oxygen consumption induced by intravenously infused nicotine or simulated cigarette smoking was probably mediated through increased mobilization and consumption of FFA.

Effect of glucagon on lipids and glucose in normal and eviscrated rats and on isolated perfused rat livers

Part 1 (in vivo): Concentrations of free fatty acids (FFA), cholesterol, amino nitrogen, glucose, and ketones in the blood, and total fat content of the liver were measured at regular intervals over a period of nine hours after the administration of 2 mg. of glucagon to male rats (fasted 48 hours prior to use). The amounts of all these metabolites in the blood, with the exception of glucose, decreased, as did the liver lipid. There was no immediate hyperglycemic effect of glucagon in the fasted animals, although a small but significant elevation in blood glucose occurred after nine hours. The hormone produced qualitatively similar changes over a six-hour period in fed rats, in which plasma total esterified fatty acids (TEFA), but not liver lipids, were measured as well. These changes persisted when the blood glucose concentrations were the same as in the controls, after a presumed period of hyperglycemia. Concentrations of lipids and amino nitrogen in the blood of eviscer-rated functionally hepatectomized rats were not significantly affected by the administration of glucagon. Part 2 (in vitro): In the isolated perfused livers, glucagon caused an increase in the perfusate blood glucose, a reduction in the increase in the cholesterol, and a decrease in the FFA concentrations. These changes are statistically highly significant. The addition of glucagon did not cause a signficant change in the TEFA in the perfusate, but did result in a significant fall in the liver TEFA content. The decrease in the amounts of lipids in blood of glucagon treated rats, and in the perfusate of isolated perfused rat livers, has been interpreted as evidence that the hormone inhibits hepatic synthesis of cholesterol and TEFA, and increases hepatic consumption of FFA, the latter possibly being due to increased FFA oxidation.