William L. Holmes

Glycerol turnover and oxidation in man

The oxidation and turnover of plasma glycerol has been studied in lean and obese, fed and starving man by means of a long-term infusion of glycerol-(14)C, and the participation of glycerol in gluconeogenesis has been determined. Under none of the experimental conditions did glycerol contribute more than 10% of the total respiratory CO(2). Glycerol turnover in fed lean subjects was 106 mmoles/min. Glycerol levels and turnover were higher in the obese subjects and with all subjects after starvation. There was a direct correlation between plasma levels and turnover values for which a regression equation was derived: y = 1556 x + 33.1, when y = turnover in micromoles per minute and x = glycerol level in micromoles per milliliter. Whereas a direct relation was established between glycerol and FFA levels, the FFA/glycerol turnover ratio was 4.7:1 in the lean group indicating incomplete hydrolysis of adipose tissue triglycerides.During starvation plasma glycerol is nearly or completely converted to glucose in the lean and obese groups, respectively. Of the new glucose formed from protein and glycerol 38% is derived from glycerol in the lean and 79% in the obese. Protein and glycerol have been shown to be adequate as precursors to supply at least as much glucose as is being oxidized per day.

Free fatty acid and glucose metabolism during increased energy expenditure and after training.

The amount of fat available as substrate to provide the energy needed for submaximal exercise is almost unlimited; therefore, it stands to reason that the organism will adapt so that it uses fat as the major energy substrate during very prolonged exercise. Nevertheless, the quantitatively smaller body stores of carbohydrate, which contain only one to two percent as many calories as the fat stores, play a very important role during exercise, since depletion of either muscle or liver glycogen will force an individual to terminate strenuous muscular work. In normal dogs during long-lasting exercise, at energy expenditures ranging from the resting state of 0.73 kcal/m2 min to a work load of 4.66 kcal/m2 min, the FFA mobilization, and participation of FFA oxidation in total energy expenditure increases. During prolonged exercise in trained dogs, 50-90% of the energy may derive from plasma FFA, while plasma glucose contributes not more than 10% to the energy expenditure. However, there is an inverse relationship between the amount of glycogen stored inside the muscle, its rate of depletion, and muscular endurance during prolonged strenuous work. Oxidation of FFA spares muscle glycogen and in this way increases work endurance.

Free fatty acid metabolism during stress: Exercise, acute cold exposure, and anaphylactic shock

Rates of turnover and oxidation of plasma free fatty acid (FFA) were determined in unanesthetized dogs during exercise, acute cold exposure and anaphylactic shock, with the aid of a technique involving the continuous infusion of albumin-bound palmitate-1-14C and the simultaneous measurement of O2 uptake, CO2 output and the specific activities of CO2 and FFA. During exercise in normal untrained dogs, plasma FFA supplied 20–30% of the energy, whereas in trained dogs 70–90% of the energy was derived from the FFA oxidation. In resting dogs at room temperature the plasma FFA level was 0.58 μEq/ml with a turnover rate of 18.6 μEq/kg/min of which 22% was immeditely oxidized and contributed 29% to the exhaled CO2. These results were compared with data obtained in pancreatectomized and thyroidectomized dogs. Acute cold exposure (temperature 4–5C) increased the FFA level and turnover rate to 1.02 μEq/ml and 28.0 μEq/kg/min, respectively, of which 33% was immedaitely oxidized, contributing 46% to the exhaled CO2. During anaphylactic shock, blood lactate increased, FFA level and turnover rate were reduced, and the fraction which was immediately oxidized was depressed markedly, i.e., 3–9% of FFA turnover. Sodium lactate infusion, which induces a blood lactate level comparable to that seen in anaphylaxis or nicotinic acid infusion, markedly decreased the level and turnover rate of FFA. However the fraction of turnover oxidized remained the same as during the preinfusion period (range of 21–40%. Exercise or the administration of norepinephrine during anaphylactic shock provided results suggesting that endogenous lactic acid interferes with FFA oxidation, whereas exogenous, lactate had no effect on this oxidation.

The effect of feeding frequency on diurnal plasma free fatty acids and glucose levels

Abstract The effect of variation in feeding frequency was noted on the diurnal plasma FFA and glucose levels in five lean males. It was shown that the single meal pattern resulted in higher mean FFA and glucose levels. The significance of these observations to the relationships between meal pattern and serum lipids and glucose tolerance is discussed.

Drugs affecting lipid metabolism VIII

Cellular Biology of Atherosclerosis.- The Cellular Pathobiology of Atherosclerosis in 1983.- Secretory Functions of the Mononuclear Phagocyte.- Risk Factors for the Development of Premature Cardiovascular Disease.- Fate of Cholesteryl Linoleyl Ether Injected into Rats as Chylomicrons, Acetylated LDL and HDL.- Hypertriglyceridemia: Lipoprotein Receptors and Atherosclerosis.- Hypertriglyceridemia and Atherosclerosis: Analysis of an Abnormal Lipoprotein System and Potential Beneficial Effects of Triglyceride Lowering Therapy.- Apolipoproteins.- The Role of Hydrophobicity in the Structure of the Human Plasma Lipoproteins.- Metabolism of Apolipoproteins and the Metabolic Heterogeneity of Apo B in the Rat.- Proapolipoprotein A-I Metabolism in the Human and the Rat.- Isolation and Characterization of the Apolipoprotein Genes.- Apoprotein Measurements.- Use of Monoclonal Antibodies in Studies of Lipoprotein Structure and Function.- Apolipoprotein E: Receptor Binding Properties.- Apolipoprotein E Mutants, Hyperlipidemia and Arteriosclerosis.- Noninvasive Assessment of Atherosclerosis.- Noninvasive Assessment of Atherosclerosis in Nonhuman Primates.- Noninvasive Assessment of Atherosclerosis: Studies in Man.- Noninvasive Atherosclerosis Assessment for Controlled Clinical Trials.- Drugs and Diet.- Strategy, Yield and Risks of Controlling Plasma Lipids in the Primary Prevention of Coronary Heart Disease.- Mechanisms of Action of Absorbable Hypolipidemic Drugs.- Dietary Factors Affecting Lipoprotein Metabolism.- Inhibition of Cholesterol Absorption by Natural Products.- Effects of Nicotinic Acid and Its Derivatives on Lipid Metabolism and Other Metabolic Factors Related to Atherosclerosis.- HMG-CoA Reductase Inhibitors.- The Role of Phosphorylation/Dephosphorylation in the Regulation of Cholesterol 7?-Hydroxylase Activity.- Calcium Antagonists and Atherosclerosis.- Management of Adherence to Prescribed Medication.- Meeting Summary.- Abstracts.- Abstracts.- Author Index.