Blood Glycerol Concentrations Research Articles

Lipid Metabolism at Two Different Walking Speeds in Obese Individuals: Pilot Study

Exercise is an important factor of obesity and overweight management. American College of Sports Medicine recommends that 150–250 minutes per week and up to 60 minutes per day of moderate‐intensity aerobic exercise should be performed for weight gain prevention or modest weight reduction. Walking is a common and relatively safe form of aerobic exercise that can easily be incorporated into weight management programs. The energy expenditure associated with walking has been reported to be either linearly or slightly exponentially related to speed. Thus, interval walking training has been developed as a novel free‐living training modality that improves physical fitness and cardiovascular risk factors in humans.PURPOSEto determine if an interval walking exercise increases fat breakdown, fat utilization, and energy expenditure to a greater extent, compared with constant walking exercise in obese adults.METHODSThis study was set as randomized crossover design. Six sedentary obese individuals (BMI ≥ 30 kg/m2 and 18–50 yrs) were recruited. Initially six subjects were randomly assigned into a constant speed walking group (CON) or an interval walking group (INT). Then, CON became INT and INT became CON. The constant speed walking consists of a single bout of 40 min walking exercise at 45% of VO2max on a treadmill. The interval walking consists of a single bout of 40 min walking exercise with cycles of alternating 3‐min slow (30% of VO2max), 3‐min moderate (45% of VO2max), and 3‐min fast (60% of VO2max) walking. Energy expenditure and fat usage were measured at rest and every 10min during walking exercises via indirect calorimetry. Blood samples were drawn at rest and every 10min during walking exercises to measure glycerol levels. Two‐way ANOVA was used to determine differences in energy expenditure and fat utilization between the groups.RESULTSThe net rates of fat utilization (g/min) and calorie expenditure (kcal/min) were not different between the groups during walking exercises. Also, blood glycerol concentrations were not different between the groups at any time points of exercise. However, the net rates of fat utilization, calorie expenditure, and blood glycerol concentrations were significantly higher at 30min and 40min of exercise, compared to those at 10min of exercise in both groups.CONCLUSIONOur data show that walking speeds might not be a primary factor to regulate fat utilization and energy expenditure during low and moderate exercise intensities. However, an increase in fat metabolism and energy expenditure during walking exercises may be attributed to the longer duration of exercise. Thus, these findings may provide a better exercise strategy to increase lipid breakdown and prevent weight gain in overweight/obese people.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The Effect of Green Tea Extract on Fat Oxidation during 1hour Arm Cycle Exercise

PURPOSE: Decaffeinated Green Tea Extract (GTE) supplementation can increase fat oxidation during leg exercise, but many people cannot perform leg exercise. The purpose of this study was to investigate the effect of GTE supplementation on fat utilization during 1h arm cycle exercise. We hypothesized that GTE supplementation will increase lipolysis and fat oxidation. METHODS: This was a randomized, controlled, triple blind study with a crossover design. 8 healthy adults (4 females, 23-37yrs) performed an incremental arm cycle test to exhaustion followed by 4 time trials at fixed workloads. After an 8h fast subjects did 1h of arm cycling at 50% Wpeak. Subjects were randomly assigned to either decaffeinated GTE (650mg, 611mg EGCG) or placebo (PLA) for 4wks. Subjects then repeated the 1hr arm cycle trial. A 4wk washout period was followed by the corresponding crossover trial. 5ml of blood were drawn pre and post exercise while respiratory gases were collected continuously. Plasma glycerol and free fatty acid (FFA) concentrations were assessed with commercially available analysis kits. The study was powered at 1-β > 95%, with α = 0.05 given a reported effect size of F = 3.39 for the time by treatment interaction. RESULTS: Mean VO2 during all 1hr trials showed no significant differences (.83-.89 ± .19-.25 L/min, p = .460). Similarly, mean total energy expenditure (EE) showed no differences across all trials (264.58 - 266.15 kcal, p = .420). The percentage of total EE from fat oxidation was higher after GTE supplementation compared to PLA, but this difference was not significant (22.83 ± 11.57 to 25.38 ± 11.3 % vs. 23.39 ± 9.97 to 20.69 ± 8.9%, p = .532). There were no significant changes in g/min of fat oxidized between treatments before and after supplementation (GTE = .11 ± .08 to .12 ± .06 vs. PLA = .10 ± .05 to .09 ± .04, p = .220. Blood Glycerol concentration increased post exercise in all trails, with no significant differences between treatments (8.55 ± 3.44 mg/dl to 8.47 ± 2.6 vs. 10.05 ± 2.86 to 8.99 ± 3.51 mg/dl, p = .527). FFA concentration was also increased post exercise for both groups with no significant difference between treatments (8.30 ± 3.8 mg/dl to 8.69 ± 2.59 vs. 9.06 ± 4.49 to 7.16 ± 3.79, p = .234). CONCLUSION: These results suggest that there is no effect of 1m GTE supplementation on fat utilization during 1hr arm cycle exercise at 50% Wpeak.

During exercise in the cold increased availability of plasma nonesterified fatty acids does not affect the pattern of substrate oxidation

Exercise in the cold was investigated to establish if the relative contribution of fat to energy expenditure is affected by the increased availability of circulating nonesterified fatty acids (NEFA). Seven men after an overnight fast cycled at approximately 70% of peak oxygen uptake for 60 minutes at an ambient temperature of 0.0°C ± 0.1°C. Fifteen minutes prior to exercise and then throughout the exercise, subjects were infused with either heparin (heparin) or saline (control). Immediately before exercise NEFA concentration (control, 0.27 ± 0.04 mmol · L −1; heparin 1.09 ± 0.13 mmol · l −1) was significantly higher ( P < .05) in the heparin trial. Pre-exercise concentration of plasma triacylglycerol (TG), blood glycerol, glucose, oxygen consumption (V̇ o 2) and respiratory exchange ratio (RER) were not significantly different between heparin and control trials. During exercise, plasma NEFA and blood glycerol concentrations were significantly higher ( P < .05) in the heparin trial, and levels of plasma TG and glucose were not different between trials. Over the exercise period rectal temperature, mean skin temperature, V̇ o 2, RER, and heart rate (HR) were not different between the 2 trials. Gross energy expenditure of cycling (control, 3.3 ± 0.1 MJ; heparin 3.3 ± 0.1 MJ), the oxidation rates of fat (control, 0.67 ± 0.05 g · min −1; heparin, 0.71 ± 0.06 g · min −1) and carbohydrate (CHO) (control, 1.68 ± 0.04 g·min −1; heparin, 1.62 ± 0.17 g · min −1) and the proportion of energy derived from fat (control, 43 ± 4%; heparin trial, 44 ± 9%) and CHO (control, 57 ± 4%; heparin trial, 56 ± 4%) were not different between the 2 trials. These findings suggest that despite increased availability of plasma NEFA, the pattern of substrate oxidation during exercise in cold temperatures does not change. This implies that uncoupling between the availability and oxidation of plasma NEFA may be a mechanism involved in the reduced oxidation of fat seen during cold exposure. Further research is needed on the utilization of intramuscular TG and circulating plasma TG-rich lipoproteins in the cold.

Effects of sympathetic inhibition on exertional dyspnoea, ventilatory and metabolic responses to exercise in normotensive humans

Augmentation of circulating noradrenaline concentration stimulates ventilation during the initial stages of exercise and this is accompanied by an increased sensation of dyspnoea and exertion. This previous study [Clark, Galloway, MacFarlane, Henderson, Aitchison and McMurray (1997) Eur. Heart J. 18, 1829-1833] suggested a link between dyspnoea, which commonly limits exercise tolerance in heart failure patients, and high circulating noradrenaline concentration in these patients. The present study investigated this relationship further using sympathetic inhibition. Ten healthy normotensive males performed 10 min of submaximal cycling exercise at approx. 70% of maximal oxygen uptake per min (VO2max) on three occasions one week apart. The first of these sessions was a familiarization session and the other two were experimental study days. On each of the study days, subjects attended the laboratory in the morning after an overnight fast and, following a resting blood sample, were administered placebo or moxonidine (0.4 mg) in a double blind cross-over design. After a 90-min absorption period, subjects undertook the exercise task. Blood was drawn, expired gas was analysed breath by breath, blood pressure, heart rate and ratings of perceived dyspnoea and exertion were obtained. Moxonidine treatment significantly reduced plasma noradrenaline concentration (P < 0.01), mean arterial pressure (P < 0.01), and blood glycerol concentration (P < 0.05), but no differences were observed in heart rate, the ventilatory response to exercise or subjective ratings of dyspnoea and exertion. This study indicates that reducing sympathetic activity does not affect ventilation, perceived dyspnoea or perceived exertion in normotensive males. Therefore it can be concluded that reducing sympathetic activity may not be an appropriate strategy to help reduce perceived dyspnoea.

Effects of sympathetic inhibition on exertional dyspnoea, ventilatory and metabolic responses to exercise in normotensive humans

Augmentation of circulating noradrenaline concentration stimulates ventilation during the initial stages of exercise and this is accompanied by an increased sensation of dyspnoea and exertion. This previous study [Clark, Galloway, MacFarlane, Henderson, Aitchison and McMurray (1997) Eur. Heart J. 18, 1829–1833] suggested a link between dyspnoea, which commonly limits exercise tolerance in heart failure patients, and high circulating noradrenaline concentration in these patients. The present study investigated this relationship further using sympathetic inhibition. Ten healthy normotensive males performed 10 min of submaximal cycling exercise at approx. 70% of maximal oxygen uptake per min (VċO2max) on three occasions one week apart. The first of these sessions was a familiarization session and the other two were experimental study days. On each of the study days, subjects attended the laboratory in the morning after an overnight fast and, following a resting blood sample, were administered placebo or moxonidine (0.4 mg) in a double blind cross-over design. After a 90-min absorption period, subjects undertook the exercise task. Blood was drawn, expired gas was analysed breath by breath, blood pressure, heart rate and ratings of perceived dyspnoea and exertion were obtained. Moxonidine treatment significantly reduced plasma noradrenaline concentration (P &lt; 0.01), mean arterial pressure (P &lt; 0.01), and blood glycerol concentration (P &lt; 0.05), but no differences were observed in heart rate, the ventilatory response to exercise or subjective ratings of dyspnoea and exertion. This study indicates that reducing sympathetic activity does not affect ventilation, perceived dyspnoea or perceived exertion in normotensive males. Therefore it can be concluded that reducing sympathetic activity may not be an appropriate strategy to help reduce perceived dyspnoea.

Insulin- and glucagon-independent effects of calcitonin gene—related peptide in the conscious dog

Calcitonin gene—related peptide (CGRP) causes vasodilation in many vascular beds, resulting in hypotension and tachycardia. The current studies were conducted in overnight-fasted conscious dogs to determine the effect of different CGRP dosages on carbohydrate metabolism and catecholamine release resulting from hemodynamic changes. During a pancreatic clamp, dogs received intraportal infusions of CGRP at 13, 26, and 52 (n = 3) or 52, 105, and 210 pmol · kg −1 · min −1 (n = 4; 60 minutes at each rate). Blood pressure decreased ( P < .05) and the heart rate and hepatic blood flow (HBF) increased a maximum of 100% and 30%, respectively ( P < .05). For the five CGRP infusion rates, arterial plasma epinephrine increased approximately 1.3-, 2.4-, 7.4-, 12-fold, and eightfold basal, respectively; norepinephrine increased about 2.3-, 3.3-, 4.1-, 4.6-, and 4.8-fold basal, respectively; and cortisol increased about twofold, 3.4-fold, fivefold, sixfold, and 6.2-fold basal, respectively. At CGRP infusion rates of 52 pmol · kg −1 · min −1 or higher, increases ( P < .05) occurred for plasma glucose, endogenous glucose production (EndoR a), and net hepatic uptake of gluconeogenic substrates (maximum change, 24 mg/dL, 1.3 mg · kg −1 · min −1, and 9.9 μmol · kg −1 · min −1, respectively). Arterial blood glycerol concentrations increased only a maximum of 30%. At the two highest CGRP infusion rates, glycerol returned to basal concentrations and arterial plasma nonesterified fatty acids (NEFAs) decreased. The increased net hepatic uptake of gluconeogenic substrates during CGRP infusion was sufficient to account for 49% to 58% of the increase in EndoR a. CGRP has no apparent direct effects on hepatic carbohydrate metabolism, but the catecholamines, at levels similar to those observed during CGRP infusion, stimulate hepatic glycogenolysis. Therefore, some factor(s) other than CGRP, probably an increase in circulating catecholamine concentrations, would appear to be responsible for at least 42% to 51% of the increase in EndoR a.

Effects of physiological hypercortisolemia on the regulation of lipolysis in subcutaneous adipose tissue.

Cortisol is known to increase whole body lipolysis, yet chronic hypercortisolemia results in increased fat mass. The main aim of the study was to explain these two apparently opposed observations by examining the acute effects of hypercortisolemia on lipolysis in subcutaneous adipose tissue and in the whole body. Six healthy subjects were studied on two occasions. On one occasion hydrocortisone sodium succinate was infused i.v. to induce hypercortisolemia (mean plasma cortisol concentrations, 1500 +/- 100 vs. 335 +/- 25 nmol/L; P < 0.001); on the other occasion (control study) no intervention was made. Lipolysis in the s.c. adipose tissue of the anterior abdominal wall was studied by measurement of arterio-venous differences, and lipolysis in the whole body was studied by constant infusion of [1,2,3-2H5]glycerol for measurement of the systemic glycerol appearance rate. Hypercortisolemia led to significantly increased arterialized plasma nonesterified fatty acid (NEFA; P < 0.01) and blood glycerol concentrations (P < 0.05), with an increase in systemic glycerol appearance (P < 0.05). However, in s.c. abdominal adipose tissue, hypercortisolemia decreased veno-arterialized differences for NEFA (P < 0.05) and reduced NEFA efflux (P < 0.05). This reduction was attributable to decreased intracellular lipolysis (P < 0.05), reflecting decreased hormone-sensitive lipase action in this adipose depot. Hypercortisolemia caused a reduction in arterialized plasma TAG concentrations (P < 0.05), but without a significant change in the local extraction of TAG (presumed to reflect the action of adipose tissue lipoprotein lipase). There was no significant difference in plasma insulin concentrations between the control and hypercortisolemia study. Site-specific regulation of the enzymes of intracellular lipolysis (hormone-sensitive lipase) and intravascular lipolysis (lipoprotein lipase) may explain the ability of acute cortisol treatment to increase systemic glycerol and NEFA appearance rates while chronically promoting net central fat deposition.

Glycerol production and utilization in humans: sites and quantitation

Liver is assumed to be the major site of glycerol uptake and fatty acid reesterification. [U-13C]glycerol was infused into ten 60 h-fasted healthy subjects. Measured were 1) blood glycerol concentrations and 13C enrichments in brachial and pulmonary arteries and in hepatic, renal, superficial, and deep forearm veins; 2) glycerol appearance rates in systemic circulation; and 3) splanchnic bed and kidney glycerol uptakes with use of balance and tracer methodology. Glycerol concentrations were one-fifth in hepatic, one-half in renal, 40% more in superficial, and the same in deep vein and pulmonary artery as in brachial artery blood. Glycerol enrichments were one-fifth in hepatic, two-thirds to three-quarters in renal and superficial veins, and the same in pulmonary as in brachial artery blood. Splanchnic glycerol uptake was 29% and kidney glycerol uptake was 17% of glycerol's rate of appearance, 5.11 mumol.min-1.kg-1. Splanchnic fatty acid uptake was 25% of calculated fatty acid release. Glycerol contributed 15% to glucose production. Most of the [13C]glycerol uptake by splanchnic bed and kidneys was incorporated into glucose. Thus, in 60 h-fasted individuals, most glycerol uptake does not occur in liver, and the extent of fatty acid reesterification in liver is in doubt.

Pseudo-pseudohypertriglyceridemia: a case of increased free glycerol without evidence for glycerol kinase deficiency

High concentrations of glycerol in plasma may result in overestimation of triglycerides in chemical and enzymatic assays. Known causes of increased glycerol concentrations in blood include glycerol-contaminated blood-collector tubes and pseudohypertriglyceridemia, a condition caused by genetic defects in the gene for glycerol kinase. We report a patient with sudden hearing loss who presented with an increased blood glycerol concentration after undergoing an oral glycerol test.

Glycerol metabolism in severe falciparum malaria

Gluconeogenesis and liver blood flow (LBF) in severe falciparum malaria were assessed from the clearance and metabolic response to intravenously administered glycerol (0.3 g/kg) and Indocyanine Green ([ICG] 0.4 mg/kg), respectively. Fasting baseline blood glycerol concentrations (mean ± SD) were significantly higher in acute malaria (133 ± 65 μmol/L, n = 14), than in convalescence (65 ± 31 μmol/L, n = 9, P = .01), but basal triacylglycerol concentrations were similar. Estimated glycerol turnover was also more than twice as high in acute malaria compared with convalescence (1.36 ± 0.87 v 0.54 ± 0.15 μmol · min −1 · kg −1, P = .015). The increment in plasma glucose (AUC 0–55 min) following glycerol infusion was greater during acute malaria compared with convalescence (median [range], +31.6 [−0.9 to + 107.6] v + 14.5 [−103 to +27.1] mmol · min · L −1, P < .05), but the insulin increments were similar ( P = .9), indicating reduced tissue insulin sensitivity. The increment in venous lactate (AUC 0–55 min) was higher in severely ill patients (17.2 [−7.8 to +53.4] mmol · min · L −1, n = 10) compared with patients with moderately severe malaria (−3.1 [−8.7 to 3.2] mmol · min · L −1, n = 4, P = .01). LBF estimated from ICG clearance was lower during acute illness than in convalescence (mean ± SD, 15.5 ± 2.3 v 18.6 ± 2.9 mL · min −1 · kg −1, P = .007) and correlated inversely with the basal venous lactate concentration ( r s = .53, P < .05). LBFs less than 15 mL · min −1 · kg −1 were associated with hyperlactatemia, and all four fatal cases had LBFs of less than 12 mL · min −1 · kg −1. Thus, despite the propensity to hypoglycemia in severe falciparum malaria, the clearance and metabolic responses to glycerol were relatively unaffected. These data also provide evidence of increased glycolysis and an association between reduced LBF and lactic acidosis in severe malaria.

Insulin sensitivity in non‐diabetic relatives of patients with non‐insulin‐dependent diabetes from two ethnic groups

Non-insulin-dependent diabetes is a heterogeneous disorder, the basis of which may differ in different ethnic groups. In order to investigate early metabolic abnormalities occurring during the development of the condition we assessed insulin secretion and insulin action in subjects predisposed to the later development of non-insulin-dependent diabetes from two different ethnic groups. Subjects were studied on two separate occasions by an oral glucose tolerance test and a short insulin tolerance test. Twenty-four glucose-tolerant first-degree relatives of patients with non-insulin-dependent diabetes (12 of European and 12 of Asian origin) were compared with 24 ethnically matched control subjects with no family history of diabetes. Insulin, proinsulin, glucose and intermediary metabolites were measured during a 75-g oral glucose tolerance test. Insulin sensitivity was assessed using a 15-minute insulin tolerance test (0.05 units/kg). Asian relatives compared to Asian controls had significantly higher fasting levels of immunoreactive insulin (83 +/- 17 vs 40 +/- 6 pmol/l, P < 0.05), which were not due to increased proinsulin. Blood glycerol concentrations were elevated (83 +/- 9 vs 51 +/- 4 mumol/l, P < 0.005), but fasting glucose and non-esterified fatty acid (NEFA) concentrations were similar. Relatives of European origin did not differ from their European controls in any of these measurements. The glucose response to oral glucose was similar in relatives and controls, irrespective of ethnic group. The insulin responses were non-significantly greater in relatives from both ethnic groups. Proinsulin levels were not significantly different. Asian relatives had higher circulating glycerol and NEFA levels after oral glucose than Asian controls, but these differences were not observed in the European group. Insulin sensitivity was reduced in the Asian relatives compared to their controls (183 +/- 7 vs 139 +/- 12 mumol/l/min, P < 0.01) but there was no difference in insulin sensitivity between the European relatives and European controls (167 +/- 11 vs 160 +/- 11 mumol/l/min). First-degree relatives of non-insulin-dependent diabetic patients of Asian, but not of European, origin are insulin insensitive in terms of both glucose metabolism and lipolysis, and have true hyperinsulinaemia. This suggests that insulin insensitivity may be an early abnormality in the development of non-insulin-dependent diabetes in the Asian population.

Carbohydrate Metabolism during Exercise in Hot and Thermoneutral Environments

This study compared the effects of moderately intense exercise in hot and thermoneutral environments on muscle glycogen and carbohydrate utilization. Well-trained, heat acclimatized cyclists (n = 7) rode at 73.6 +/- 1.1% maximal oxygen consumption for 60 min in a thermoneutral room (23.5 +/- 0.6 degrees C, 52.7 +/- 2.9 relative humidity) or an environmental chamber (33.7 +/- 0.1 degrees C, 49.1 +/- 1.8% relative humidity). During each exercise bout, the subjects received 125 ml of water every 15 min. Muscle biopsies from the vastus lateralis were obtained prior to and following each exercise bout. Exercise in the heat significantly elevated rectal temperature and heart rate above and reduced body weight and plasma volume below that produced by exercise in a thermoneutral environment. Plasma glucose and blood lactate concentrations were similar between treatments prior to exercise, but increased to a greater concentration (p < 0.05) when exercise was performed in the heat. No differences between treatments were found for blood glycerol or free fatty acid concentrations, carbohydrate oxidation or muscle glycogen utilization. These results suggest that moderately intense exercise in the heat, as opposed to a thermoneutral environment, does not increase the rate of muscle glycogenolysis or carbohydrate oxidation in well conditioned, heat acclimatized subjects.

Twenty-four hour C-peptide and insulin secretion rates and diurnal profiles of glucose, lipids and intermediary metabolites in cirrhosis.

1. To examine the contributions of hypersecretion and decreased insulin clearance to the hyperinsulinaemia of cirrhosis, insulin secretion was calculated over the day from serum C-peptide concentrations and C-peptide metabolic clearance rate. The latter was measured during infusions of recombinant human C-peptide. In cirrhotic patients (n = 9) insulin secretion rate was twice that of normal control subjects (n = 10), both in the basal state [02.00-07.00 hours, 15.7 +/- 2.1 (mean +/- SEM) nmol/h (2.6 +/- 0.4 units/h) versus 7.0 +/- 0.9 nmol/h (1.2 +/- 0.2 units/h), P < 0.002] and over 24 h [787 +/- 93 nmol (132 +/- 16 units) versus 346 +/- 34 nmol (58 +/- 6 units), P < 0.001]. However, the area under the serum insulin concentration curve was approximately six times greater in the cirrhotic patients (24 h basal, 6.3 +/- 1.0 versus 1.1 +/- 0.3 nmol l-1 h, P < 0.001; 24 h total, 21.7 +/- 3.2 versus 3.7 +/- 0.7 nmol l-1 h, P < 0.001). Thus, despite impairment of insulin clearance there is continuing hypersecretion of insulin in cirrhosis. 2. The relationship of carbohydrate and lipid metabolism with insulin secretion was assessed. In cirrhotic patients, 24 h blood glucose profiles showed a worsening of glucose tolerance over breakfast, despite greater insulin secretion compared with other meals, suggesting that the insulin insensitivity of cirrhosis is worse at this time. 3. Cirrhotic patients showed impaired suppression of blood glycerol levels after meals but normal suppression of serum non-esterified fatty acid concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise metabolism at different time intervals after a meal

To determine how long a meal will affect the metabolic response to exercise, nine endurance-trained and nine untrained subjects cycled for 30 min at 70% of peak O2 consumption (VO2 peak) 2, 4, 6, 8, and 12 h after eating 2 g carbohydrate/kg body wt. In addition, each subject completed 30 min of cycling 4 h after the meal at an intensity that elicited a respiratory exchange ratio (RER) of 0.94-0.95. During exercise after 2 and 4 h of fasting, carbohydrate oxidation was elevated 13-15% compared with the response to exercise after an 8- and 12-h fast (P less than 0.01). The increase in blood glycerol concentration during exercise (30 to 0 min) was linearly related to the length of fasting (r = 0.99; P less than 0.01). In all subjects, plasma glucose concentration declined 17-21% during exercise after 2 h of fasting (P less than 0.01). Plasma glucose concentration also declined (15-25%) during exercise in the trained subjects after 4 and 6 h of fasting (P less than 0.05) but did not change in the untrained subjects. However, the decline in plasma glucose concentration was similar (14%) in the two groups when the exercise intensity was increased in the trained subjects (i.e., 78 +/- 1% VO2 peak) and decreased in the untrained subjects (i.e., 65 +/- 3% VO2 peak) to elicit a similar RER.(ABSTRACT TRUNCATED AT 250 WORDS)

Contribution of glycerol and alanine to basal hepatic glucose production in the genetically obese (fa/fa) rat

Increased hepatic glucose production has been reported to occur in the insulin-resistant genetically obese fa/fa rats. The possible existence of an increased basal gluconeogenesis in obese rats was investigated, upon comparing the metabolic fate of glycerol and alanine in liver of fed anaesthetized lean and genetically obese (fa/fa) rats. Glycerol turnover rate in obese animals was 3 times that of the lean. This increase in glycerol turnover rate was associated with an increase in blood glycerol levels in obese animals. The contribution of glycerol to glucose production was significantly increased in obese animals. In contrast, the contribution of alanine to the hepatic glucose production was similar to lean and obese animals. A higher incorporation of glucose, glycerol and alanine into hepatic lipids was observed in obese animals than in controls. It is concluded that in fed genetically obese (fa/fa) rats the high blood glycerol concentrations is a major driving force for the increased basal hepatic conversion of this substrate into glucose.

Enhanced thermogenic response to epinephrine after 48-h starvation in humans

The effects of 48-h starvation on the physiological responses to a 30-min infusion of epinephrine at 25 ng.min-1.kg body wt-1 were studied in 11 normal-weight healthy young subjects. Starvation led to considerable alterations in basal metabolism including a significant (mean 3.6%) increase in resting metabolic rate. During the infusions, plasma epinephrine concentration rose less in the starved state (+1.47 nmol/l) than in the normally fed state (+1.73 nmol/l) (SE 0.06 nmol/l; P less than 0.05). The maximum increments (mean +/- SE) in heart rate induced by epinephrine were 11.9 +/- 1.3 beats/min in the normally fed state and 20.1 +/- 2.0 beats/min in the starved state (P less than 0.001); the corresponding mean increments in blood glycerol concentration were 0.07 and 0.14 mmol/l (SE 0.01 mmol/l; P less than 0.01). The increase in the metabolic rate above base line during the final 10 min of the epinephrine infusion was 0.58 +/- 0.18 kJ/min in the normally fed state and 0.78 +/- 0.14 kJ/min in the starved state (P less than 0.01). The chronotropic, lipolytic, and thermogenic effects of infused epinephrine were therefore enhanced by prior starvation, despite the lower plasma epinephrine levels.

Metabolic Abnormalities in Obese Patients with Impaired Glucose Tolerance

It is not clear whether the glucose tolerance test diagnosis of Impaired Glucose Tolerance introduced in the recent revisions of diagnostic criteria is associated with abnormalities of intermediary metabolism other than glucose. Intermediary metabolite concentrations have therefore been studied fasting and in response to oral glucose in 35 patients referred with morbid obesity accompanied by either normal glucose tolerance (18 patients) or Impaired Glucose Tolerance (17 patients). When fasting obese patients with Impaired Glucose Tolerance had significantly higher blood total ketone body concentrations, 0.24 (0.19-0.30) vs 0.14 (0.12-0.16) mmol l-1 (antilog of mean-SE to mean + SE) (p less than 0.05), and lower blood glycerol concentrations, 0.14 +/- 0.01 vs 0.18 +/- 0.01 mmol l-1 (mean +/- SE) (p less than 0.05), than obese patients with normal glucose tolerance. There were no significant differences in fasting insulin, 16 (15-18) vs 14 (12-15) mU l-1, or glucose levels, 5.3 +/- 0.2 vs 5.1 +/- 0.2 mmol l-1. After oral glucose there was an exaggerated rise in glucose, insulin, lactate, and pyruvate in patients with Impaired Glucose Tolerance.

Metabolic responses to intense exercise in lean and obese subjects.

Sustained elevations of plasma glucose and insulin concentrations follow intense (80% maximum oxygen uptake) exercise performed in the postabsorptive state. To provide insights into possible mechanisms and influence of obesity, 8 lean and 12 obese subjects [106 +/- 11% (SD) and 193 +/- 31% of reference table weight, respectively] eating previously isocaloric diets were exercised to exhaustion (7 +/- 3 min) on a cycle ergometer, then followed for 60 min of recovery. The obese subjects at rest had slightly increased plasma glucose and insulin and elevated blood glycerol concentrations. Both lean and obese subjects had little or no changes in plasma glucose or insulin during exercise, but the increases during the recovery period were greater and/or sustained longer in the obese. Such results raise the possibility of transient hepatic insulin resistance after exercise and are possibly relevant to restoration of depleted muscle glycogen. Both groups had a marked fall in plasma FFA during exercise; the reduction was sustained in the lean but not in the obese subjects. Blood glycerol increased during the recovery period to higher values in the obese than in the lean subjects. Plasma norepinephrine increased about 4-fold in both groups, returning promptly to preexercise values. In contrast, the exercise-induced increment in plasma epinephrine [values at exhaustion, 933 +/- 548 vs. 1970 +/- 787 pmol/L; P less than 0.005] was markedly attenuated in the obese subjects. Thus, the obese subjects had exercise-induced changes in glucose and inulin metabolism consistent with greater postexercise insulin resistance, despite an impaired plasma epinephrine response to intense exercise.

Following weight loss in massively obese patients correction of the insulin resistance of fat metabolism is delayed relative to the improvement in carbohydrate metabolism

Intermediary metabolite and serum insulin concentrations have been measured during incremental intravenous low-dose insulin infusion in massively obese patients before, and 3 months and 12 months after gastroplasty. Fasting blood glucose was similar on the three occasions, but fasting serum insulin was significantly higher preoperatively and showed a progressive fall with weight loss. Significant negative linear correlations were found between serum insulin and blood glucose, plasma nonesterified fatty acids, blood glycerol and blood total ketone bodies concentrations. The insulin-glucose dose-response curve showed a significant left shift at 3 months with a further significant improvement at 12 months. No significant change in the responses for nonesterified fatty acids, glycerol, and ketone bodies was observed at 3 months, but all three showed a significant left shift at 12 months. Massively obese patients are resistant to the action of insulin on carbohydrate and fat metabolism. Weight loss following gastroplasty results in an improvement in sensitivity to insulin, which is evident earlier in carbohydrate metabolism than in fat metabolism.

The energy cost of triglyceride-fatty acid recycling in nonobese subjects after an overnight fast and four days of starvation

The basal blood glycerol concentration was determined and the rate of glycerol turnover was assessed by a nonradioactive infusion technique in six healthy nonobese adults after an overnight fast and again after four days of total starvation. Simultaneously, estimates of total energy expenditure and net fat oxidation were made from measurements of oxygen consumption, carbon dioxide production, and urinary nitrogen excretion. The data were combined to provide quantitative estimates of the activity of the triglyceride/fatty acid cycle. The basal concentration of glycerol in venous blood rose from a mean value of 54 ± 8 μmol/L (SEM) before starvation to 154 ± 5 μmol/L on day 4 of starvation. Glycerol turnover rates correlated well with the basal blood glycerol concentration ( r = .95) and increased from a mean value of 115 ± 17 μmol/min before starvation (equivalent to mobilization of about 3.95 kJ triglyceride/min) to 304 ± 20 μmol/min (equivalent to mobilization of about 18.41 kJ/min). The estimated rate of net fat oxidation was 3.00 ± 0.47 kJ/min before starvation and 4.00 ± 0.14 kJ/min on day +4 of starvation. The rate of triglyceride energy recycling or rate of deposition of triglyceride energy into fat stores was calculated from the difference in the rate of fat energy mobilization and the rate of energy released during net fat oxidation. The values were found to be 0.94 ± 0.26 kJ/min before starvation and 6.29 ± 0.54 kJ/min on day +4 of starvation. The mean energy cost associated with cycling of this amount of energy in the triglyceride/fatty acid cycle was calculated to be 0.018 kJ/min (0.36% of resting energy expenditure) before starvation and 0.12 kJ/min (2.49% of resting energy expenditure) after four days of starvation. It is concluded that although the activity of the triglyceride/fatty acid cycle increases considerably during starvation, the energy expended in driving the cycle is only a small proportion of total energy expenditure.