Plasma Glycerol Research Articles

Associations between circulating adiponectin and selected plasma biochemical variables in physically active young men and women

Associations between circulating adiponectin and selected plasma biochemical variables in physically active young men and women Study aim: To evaluate the relationships between circulating adiponectin and FFA, and other biochemical variables (glycerol, glucose and insulin) in young, healthy non-obese men and women. Material and methods: A group of 53 male and 54 female students participated in the study. The following compounds were determined in plasma: free fatty acids (FFA), glucose and glycerol (colorimetrically), and insulin and adiponectin (by immunoassay). Insulin resistance index (HOMA-IR) was calculated from fasting insulin and glucose concentrations. Results: Mean plasma glucose was slightly lower (p<0.01), and plasma insulin and HOMA-IR markedly higher (p<0.01 - 0.001) in female than in male subjects. Percent body fat was positively correlated with plasma FFA in both groups (p<0.01), but with plasma glycerol (p<0.001) in female students only. Plasma adiponectin was negatively correlated with percent body fat (p<0.02), plasma glycerol (p<0.001) and FFA (p<0.05) in female subjects only. Conclusions: Gender-related differences in body fat may affect the relationship between adiponectin and indices of lipid metabolism.

Growth, body composition and metabolism at neonatal and adolescent life stages in low birth weight offspring

Human epidemiological studies have linked presumed fetal malnutrition leading to low birth weight with the subsequent development of metabolic syndrome. Using our established ovine model of late onset placental growth restriction, we assessed the impact of poor prenatal fetal nutrient supply on birth weight, growth, body composition and metabolism in both genders during neonatal and adolescent life. Singleton-bearing adolescent dams were fed control (C) or high (2.25 · C) nutrient intakes during pregnancy to induce normal or compromised placental size, respectively (1) . The resulting normal (N; twelve male and twelve female) or placentally growth-restricted (PGR; nine male and sixteen female) lambs suckled their ad libitum fed mothers until weaning at 11 weeks of age. Thereafter, offspring were individually housed and had ad libitum access to the same nutrient dense complete diet. Lamb growth rates were measured throughout and body composition was determined by Dual energy X-ray absorptiometry at weaning and at 35 weeks of age (adolescence). At 7 weeks of age, lambs were fasted for 3 h prior to an intravenous glucose tolerance test (GTT). Three baseline blood samples were collected and metabolite responses measured at + 5, 10, 15, 20, 30, 45, 60, 90 and 120 min relative to glucose administration (0.25 g/kg body weight). A second GTT was performed at 28 weeks of age after an overnight fast (0.5 g glucose/kg). Plasma was analysed for insulin, glucose, NEFA and glycerol. PGR males and females were 35 and 49 % lighter than N lambs at birth, respectively, and had reduced girth and height (all P < 0.001). Fractional growth rate to weaning was elevated in PGR v. N groups (P < 0.001), was highest in PGR males (P < 0.03) and was inversely correlated with birth weight (r = - 0.887, P < 0.001). Dual energy X-ray absorptiometry assessment of body composition at weaning revealed reduced bone mineral density (P < 0.02) and increased total fat % (P < 0.001) in PGR compared with N lambs (bone mineral density; 0.570.014 v. 0.620.010 g/cm, and fat; 24.10.95 v. 16.60.77 %, no effect of gender). Fractional growth rate from weaning to adolescence remained higher and height remained lower in PGR v. N lambs (P < 0.001) and both were greater in males than females (P < 0.002). At 35 weeks, bone mineral density remained higher in PGR than N lambs (0.730.014 v. 0.860.012 g/cm, P < 0.001) and females were fatter than males (31.10.92 v. 20.20.88%, P < 0.001). Fasting plasma insulin, glucose, NEFA and glycerol were higher in PGR than N lambs (P ranging from < 0.035 to < 0.001) at both 7 and 28 weeks of age. Insulin secretion after GTT was higher in PGR v. N groups at both ages (P < 0.02) and was greatest in PGR males. NEFA and glycerol concentrations after GTT were similarly increased (P < 0.02) in PGR lambs at both ages. At 28 weeks, but not at 7 weeks, glucose area under the curve after GTT was higher in PGR than N lambs (P < 0.02), indicative of glucose intolerance. Therefore, low birth weight offspring of both genders exhibit rapid postnatal catch-up growth and altered body composition in our animal model. This was associated with increased insulin secretion, glucose intolerance and altered indices of fat metabolism during neonatal to adolescent life, all of which may presage poor health in adult life.

Influence of housing type and age in female pigs. 2. Effects on biochemical indicators of fat metabolism and the fatty acid profile of belly fat and back fat depots

Weaning pigs into deep-litter (D) housing systems and then moving them into conventional (C) housing facilities affects the growth paths of the pigs and can result in differences in carcass composition which may be explained by altered fat metabolism. To examine this proposition experimentally, 160 female Large White × Landrace pigs were obtained at 3 weeks of age, average liveweight 5.5 ± 0.08 kg and were stratified by weight to four treatments. The treatments consisted of two housing treatments, C or D, across two growth periods: (i) early (3–13 weeks of age); and (ii) late (13–24 weeks of age). At ~13 weeks of age eight pigs per experimental treatment (n = 32) were slaughtered and the remaining pigs (n = 128) moved to new pens where they were housed until slaughter at ~24 weeks of age. To 13 weeks of age, the effect of housing type on lipogenesis did not reach significance (P &gt; 0.05). At 24 weeks of age there were some treatment differences in fatty acid profile (P ≤ 0.05) and the concentration of plasma glycerol (P = 0.002) and non-esterified fatty acids (P = 0.019). There were trends for lipogenic enzyme activity to differ between treatments also (P &lt; 0.100). Results suggested fat deposition was lower in D-finished pigs compared with C-finished pigs, rejecting the hypothesis that D-finished pigs would be fatter. However, most of the differences in the biochemical measurements were explained by the significant reduction in growth that occurred when pigs changed housing environments, rather than as an effect of the housing environment itself. Indicators of lipogenesis suggested that lipogenic rate was lowest in pigs moved from C to D housing compared with other treatment groups that had remained within the same housing, C or D, throughout the experiment or had moved from D housing to C housing at 13 weeks of age.

Glycerol loss to water exceeds glycerol catabolism via glycerol kinase in freeze-resistant rainbow smelt (Osmerus mordax)

Rainbow smelt accumulate high amounts of glycerol in winter. In smelt, there is a predictable profile of plasma glycerol levels that starts to increase in November (<5 μmol/ml), peaks in mid-February (>200 μmol/ml), and thereafter decreases to reach the initial levels in the beginning of May. The aim of this study was to investigate the respective role of the two main mechanisms that might be involved in glycerol clearance from mid-February: 1) breakdown of glycerol to glycerol-3-phosphate through the action of the glycerol kinase (GK) and 2) direct loss toward the environment. Over the entire glycerol cycle, loss to water represents a daily loss of ∼10% of the total glycerol content of fish. GK activities were very low in all tissues investigated and likely have a minor quantitative role in the glycerol cycle. These results suggest that glycerol levels are dictated by the rate of glycerol synthesis (accelerated and deactivated during the accumulation and decrease stages, respectively). Although not important in glycerol clearance, GK in liver might have an important metabolic function for other purposes, such as gluconeogenesis, as evidenced by the significant increase of activity at the end of the cycle.

Studies on the anti-obesity activity of zinc-α2-glycoprotein in the rat

To investigate the anti-obesity effect of the adipokine zinc-α(2)-glycoprotein (ZAG) in rats and the mechanism of this effect. Mature male Wistar rats (540 ± 83 g) were administered human recombinant ZAG (50 μg per 100 g body weight given intravenously daily) for 10 days, while control animals received an equal volume of phosphate-buffered saline (PBS). Animals treated with ZAG showed a progressive decrease in body weight, without a decrease in food and water intake, but with a 0.4 °C rise in body temperature. Body composition analysis showed loss of adipose tissue, but an increase in lean body mass. The loss of fat was due to an increase in lipolysis as shown by a 50% elevation of plasma glycerol, accompanied by increased utilization of non-esterified fatty acids, as evidenced by the 55% decrease in plasma levels. Plasma levels of glucose and triglycerides were also reduced by 36-37% and there was increased expression of the glucose transporter 4 in both skeletal muscle and adipose tissue. Expression of the lipolytic enzymes adipose triglyceride lipase and hormone-sensitive lipase in the white adipose tissue (WAT) were increased twofold after ZAG administration. There was almost a twofold increased expression of uncoupling proteins 1 and 3 in brown adipose tissue and WAT, which would contribute to increased substrate utilization. Administration of ZAG increased ZAG expression twofold in the gastrocnemius muscle, BAT and WAT, which was probably necessary for its biological effect. These results show that ZAG produces increased lipid mobilization and utilization in the rat.

The effect of training on plasma L-carnitine metabolism in purebred Arabian horses

1. Dynamic change of free serum L-carnitine concentration in relation to age, sex, and exercise in Anglo-Arabian Thoroughbred horses Francesca Arfuso, Claudia Giannetto, Elisabetta Giudice, Francesco Fazio, Giuseppe Piccione Journal of Equine Veterinary Science CrossRef

Effects of capsinoid ingestion on energy expenditure and lipid oxidation at rest and during exercise

BackgroundThe thermogenic and metabolic properties of capsinoids appear to mimic those of the more pungent sister compound capsaicin. However, few data exist on how capsinoid ingestion affects energy expenditure in humans and no data exist on its interaction with exercise. We aimed to determine how ingestion of capsinoids affected energy expenditure, lipid oxidation and blood metabolites at rest and during moderate intensity exercise.MethodsTwelve healthy young men (age = 24.3 ± 3 yr, BMI = 25.5 ± 1.7 kg·m-2) were studied on two occasions in a double-blind design following ingestion of either placebo or 10 mg of purified capsinoids at rest, after 90 min of cycling at 55% VO2 peak, and for 30 min into recovery. Subjects ingested the capsules 30 min prior to exercise.ResultsAt rest, following ingestion of capsinoids, we observed increases in VO2 and plasma norepinephrine levels, and decreases in concentrations of serum free fatty acids, plasma glycerol and the respiratory exchange ratio (all P < 0.05). At exercise onset, we observed a blunted accumulation of blood lactate with capsinoid ingestion vs. placebo (P < 0.05). There were no other significant differences between the conditions during or post-exercise.ConclusionThe ingestion of 10 mg of capsinoids increased adrenergic activity, energy expenditure, and resulted in a shift in substrate utilization toward lipid at rest but had little effect during exercise or recovery. The changes we observed confirm previous data on the thermogenic and metabolic effects of capsinoids at rest and further promote its potential role as an adjunct weight loss aid, in addition to diet and exercise.

Effects of Exposure to a 128-mT Static Magnetic Field on Glucose and Lipid Metabolism in Serum and Skeletal Muscle of Rats

Increasing environmental pollution may participate in the growing incidence of metabolic disorders. Static magnetic fields (SMFs) are an emerging environmental health issue due to increased exposure in residential and commercial areas; however, their metabolic effects in serum and skeletal muscle are largely unknown. The aim of this study was to investigate the effect of SMF exposure on glucose and lipid metabolism in serum and skeletal muscles of rats. Twelve 6- to 7-week-old male Wistar rats were randomly divided into two groups: rats exposed to 128 mT SMF and sham-exposed rats. This moderate-intensity exposure was performed for 1 h/day for 15 consecutive days. Animals exposed to 128 mT SMF displayed significant changes in both glucose (i.e., increases in plasma glucose and lactate and decrease in plasma insulin levels) and lipid (i.e., increases in plasma glycerol, cholesterol and phospholipids but not triglyceride levels) metabolism. During intraperitoneal glucose tolerance tests, SMF-exposed rats displayed significantly higher hyperglycemia compared to sham-exposed rats despite similar insulin levels in both groups. In tissues, SMF exposure induced significant alterations in enzyme activities only in glycolytic muscles and caused a significant decrease in quadriceps and liver glycogen content together with increased phospholipid levels. This study provides evidence that subacute SMF exposure of moderate intensity induces important alterations of glucose and lipid metabolisms, which deserve further investigations to evaluate long-term consequences.

Adipose Acyl-CoA Synthetase-1 Directs Fatty Acids toward β-Oxidation and Is Required for Cold Thermogenesis

Long-chain acyl-CoA synthetase-1 (ACSL1) contributes 80% of total ACSL activity in adipose tissue and was believed to be essential for the synthesis of triacylglycerol. We predicted that an adipose-specific knockout of ACSL1 (Acsl1(A-/-)) would be lipodystrophic, but compared to controls, Acsl1(A-/-) mice had 30% greater fat mass when fed a low-fat diet and gained weight normally when fed a high-fat diet. Acsl1(A-/-) adipocytes incorporated [(14)C]oleate into glycerolipids normally, but fatty acid (FA) oxidation rates were 50%-90% lower than in control adipocytes and mitochondria. Acsl1(A-/-) mice were markedly cold intolerant, and beta(3)-adrenergic agonists did not increase oxygen consumption, despite normal adrenergic signaling in brown adipose tissue. The reduced adipose FA oxidation and marked cold intolerance of Acsl1(A-/-) mice indicate that normal activation of FA for oxidation in adipose tissue in vivo requires ACSL1. Thus, ACSL1 has a specific function in directing the metabolic partitioning of FAs toward beta-oxidation in adipocytes.

Bisphenol A Exposure during Pregnancy Disrupts Glucose Homeostasis in Mothers and Adult Male Offspring

BackgroundBisphenol A (BPA) is a widespread endocrine-disrupting chemical used as the base compound in the manufacture of polycarbonate plastics. In humans, epidemiological evidence has associated BPA exposure in adults with higher risk of type 2 diabetes and heart disease.ObjectiveWe examined the action of environmentally relevant doses of BPA on glucose metabolism in mice during pregnancy and the impact of BPA exposure on these females later in life. We also investigated the consequences of in utero exposure to BPA on metabolic parameters and pancreatic function in offspring.MethodsPregnant mice were treated with either vehicle or BPA (10 or 100 μg/kg/day) during days 9–16 of gestation. Glucose metabolism experiments were performed on pregnant mice and their offspring.ResultsBPA exposure aggravated the insulin resistance produced during pregnancy and was associated with decreased glucose tolerance and increased plasma insulin, triglyceride, and leptin concentrations relative to controls. Insulin-stimulated Akt phosphorylation was reduced in skeletal muscle and liver of BPA-treated pregnant mice relative to controls. BPA exposure during gestation had long-term consequences for mothers: 4 months postpartum, treated females weighed more than untreated females and had higher plasma insulin, leptin, triglyceride, and glycerol levels and greater insulin resistance. At 6 months of age, male offspring exposed in utero had reduced glucose tolerance, increased insulin resistance, and altered blood parameters compared with offspring of untreated mothers. The islets of Langerhans from male offspring presented altered Ca2+ signaling and insulin secretion. BrdU (bromodeoxyuridine) incorporation into insulin-producing cells was reduced in the male progeny, yet β-cell mass was unchanged.ConclusionsOur findings suggest that BPA may contribute to metabolic disorders relevant to glucose homeostasis and that BPA may be a risk factor for diabetes.

Effect of Resistance Exercise on Indices of Fatigue

The ergogenic effects of carbohydrate ingestion on aerobic exercise have been well established; however, the literature is mixed regarding resistance training. PURPOSE: To determine the ergogenic effects of carbohydrate ingestion on isometric leg exercise, plasma glucose (PG) responses, plasma free fatty acid (FFA), plasma glycerol, and blood lactate responses (La) during a selected resistance protocol. METHODS: Six male subjects with a minimum of three years of bodybuilding and/or power lifting experience performed one mock trial and two randomly assigned exercise trials in which either a glucose polymer (GP) solution (0.17g·kg-1 body mass) or placebo (P) was administered in a double-blind fashion. Participants performed single-leg isometric contractions at 50% of one repetition maximum (1RM) for 20 seconds (s), followed by 40 s of rest between contractions, until failure occurred. Failure was defined as the inability to sustain target force for 5 consecutive seconds. The decrease in force generating capacity was tested from brief maximal voluntary contractions and short bursts of 60 Hz stimulation applied at 5 min intervals. Slope of fatigue was measured using a strain gauge type load cell, which sent an amplified signal to a desktop computer for interpretation. Plasma glucose, FFA, glycerol, and La were measured prior to testing, midway through the protocol, immediately post-exercise, and at five min post-exercise. RESULTS: A statistical evaluation of temporal changes linear regression analysis revealed a more linear slope in the GP than P trial (GP = -0.0594 ± -0.0299 and P = -0.0300 ± -0.0109). This result was significant (p =.028). A 2 × 4 ANOVA with repeated measures revealed PG and La were significantly elevated in the GP protocol. No significant differences were observed between the treatments for FFA and glycerol concentrations. Finally, a Pearson's correlation revealed a significant relationship between force production and blood lactate (r = -0.689, p <.05). CONCLUSIONS: The results suggest that the ingestion of a liquid carbohydrate supplement prior to and intermittently throughout single-leg isometric lower body resistance training protocols appears to elevate blood glucose levels and provide an ergogenic effect that is reflected by a more linear slope of fatigue.

Use of crude glycerol, a biodiesel coproduct, in diets for lactating sows1,2

An experiment was conducted to evaluate the effect of dietary crude glycerol in lactating sow diets on sow and litter performance under heat stress conditions. Mixed parity (range = 0 to 13) sows (n = 345; 253 +/- 24 kg of BW) were assigned randomly within gestation housing location and parity to 1 of 4 dietary treatments. Treatments consisted of a corn-soybean-based control diet (CON) and 3, 6, or 9% glycerol added at the expense of corn and soybean meal. Liquid crude glycerol was incorporated in the complete diet at the time of mixing. Dietary treatments were imposed on d 109 of gestation (2.25 kg/d) when sows were moved into farrowing rooms. Heat index during lactation in farrowing rooms exceeded 25 degrees C for all sows. At farrowing, sows were allowed ad libitum access to feed throughout lactation. Dietary treatment tended (P = 0.08) to influence ADFI of sows (CON = 6.04 kg/d; 3% = 6.21 kg/d; 6% = 5.69 kg/d; 9% = 6.00 kg/d; pooled SE = 0.18). Up to 9% crude glycerol in the diet had no effect on sow BW and backfat loss, weaning-to-estrus interval, preweaning mortality of piglets, and ADG of piglets. Increasing dietary glycerol linearly reduced (P = 0.10) litter size at weaning (CON = 9.50; 3% = 9.60; 6% = 9.36; 9% = 9.39; pooled SE = 0.08). Daily water consumption was not affected by dietary treatment. Crude glycerol did not affect respiration rates or rectal body temperatures, indicating no efficacy in reducing heat stress of sows. Plasma glycerol concentrations increased linearly (P < 0.05) as dietary crude glycerol increased (CON = 1.21 microM; 3% = 1.69 microM; 6% = 7.21 microM; 9% = 29.04 microM; pooled SE = 1.58), but plasma glucose concentrations were not affected. Crude protein content of the milk of sows was not affected (P = 0.16) by dietary treatment. Dry matter (P = 0.07) and crude fat (P = 0.09) content of the milk of the sows tended to increase linearly (DM basis: CON = 17.84%; 3% = 18.43%; 6% = 18.98%; 9% = 18.48%; pooled SE = 0.34; crude fat: CON = 4.78%; 3% = 4.91%; 6% = 5.50%; 9% = 5.24%; pooled SE = 0.30), whereas milk ash concentration tended (P = 0.09) to decrease linearly with increasing dietary glycerol (CON = 0.77%; 3% = 0.79%; 6% = 0.74%; 9% = 0.74%; pooled SE = 0.02). Increasing dietary crude glycerol linearly increased (P < 0.05) lactose concentration in the milk of sows (CON = 5.16%; 3% = 5.30%; 6% = 5.43%; 9% = 5.46%; pooled SE = 0.10). Results from this study indicate that lactating sows fed diets containing up to 9% crude glycerol perform similarly to sows fed a standard corn-soybean meal diet.

Gender specific regulation of hepatic aquaglyceroporin 9 and glycerol kinase expression

Increased hepatic glucose production plays a pivotal role in the pathophysiology of diabetes. AQP9 has been suggested to facilitate the transport of glycerol into hepatocytes where glycerol kinase (GK) catalyses the initial step for its conversion into either glucose or glycerolipids. Hence, the regulation of AQP9 and thereby glycerol uptake could be a potential modulator of hepatic glucose production. This study aims to investigate the role of gender in regulation of hepatic AQP9 and GK protein. Immunoblotting showed that starvation of male rats resulted in increased hepatic AQP9 and GK abundance, whereas, starved female rats displayed no increase in AQP9 or GK. In contrast, plasma glycerol levels were doubled in female rats in response to starvation, whereas no statistically significant changes were found in male rats. Interestingly, immunoblotting revealed that castration of male rats resulted in a 1.5 fold increase in hepatic AQP9 expression, but a decrease in GK abundance. This was accompanied by a marked reduction in plasma glycerol together with a small but significant increase in plasma glucose when compared with controls. We conclude that sexual dimorphism exists in hepatic glycerol handling in response to starvation and that castration of male rats has a diverse effect upon liver abundance of AQP9 and GK.Supported by the Danish National Research Foundation

Adipose triglyceride lipase plays a key role in the supply of the working muscle with fatty acids

FAs are mobilized from triglyceride (TG) stores during exercise to supply the working muscle with energy. Mice deficient for adipose triglyceride lipase (ATGL-ko) exhibit defective lipolysis and accumulate TG in adipose tissue and muscle, suggesting that ATGL deficiency affects energy availability and substrate utilization in working muscle. In this study, we investigated the effect of moderate treadmill exercise on blood energy metabolites and liver glycogen stores in mice lacking ATGL. Because ATGL-ko mice exhibit massive accumulation of TG in the heart and cardiomyopathy, we also investigated a mouse model lacking ATGL in all tissues except cardiac muscle (ATGL-ko/CM). In contrast to ATGL-ko mice, these mice did not accumulate TG in the heart and had normal life expectancy. Exercise experiments revealed that ATGL-ko and ATGL-ko/CM mice are unable to increase circulating FA levels during exercise. The reduced availability of FA for energy conversion led to rapid depletion of liver glycogen stores and hypoglycemia. Together, our studies suggest that ATGL-ko mice cannot adjust circulating FA levels to the increased energy requirements of the working muscle, resulting in an increased use of carbohydrates for energy conversion. Thus, ATGL activity is required for proper energy supply of the skeletal muscle during exercise.

Effect of Carbohydrate- and Protein-rich Meals on Exercise-induced Activation of Lipolysis in Obese Subjects

Exercise is an important part of obesity treatment concepts to support fat mobilisation from adipose tissue and also fat oxidation nolich is impaired in obese subjects. In normal weight subjects it is well known that stimulation of plasma insulin levels by a carbohydrate meal can inhibit lipolysis and subsequent fat oxidation. Since obese subjects frequently have elevated basal and postprandial insulin levels the effect of carbohydrate- and protein-rich test meals on exercise-induced activation of lipolysis is of special interest. Twenty obese subjects performed bicycle exercise for 30 min in the fasted state, 30 min after a carbohydrate-or a protein-rich meal, and 120 min after the carbohydrate meal (n=12), respectively, at low intensity. Activation of lipolysis was assessed by plasma glycerol levels. In addition, plasma insulin, glucose, and lactate concentrations were determined. In comparison to the fasted state, the carbohydrate meal suppressed activation of lipolysis. Following the protein meal, exercise led to an attenuated but significant increase of glycerol levels. A similar rise was observed when the carbohydrate meal was ingested 2 h prior to the exercise bout. To improve exercise-induced lipolysis and subsequent fat oxidation during low-intensity exercise obese subjects should not ingest carbohydrates immediately before exercise. Hunger sensations should be satisfied with protein-rich food. When carbohydrates are consumed 2 h prior to exercise its lipolytic effect is comparable to the protein meal. These data are useful in every day dietary counselling and might help to improve weight loss during obesity treatment.

Water Extract of Houttuynia cordata Thunb. Leaves Exerts Anti-Obesity Effects by Inhibiting Fatty Acid and Glycerol Absorption

Houttuynia cordata Thunb. is used in folk medicine for diuresis and detoxification. However, it has not yet been reported to have an anti-obesity effect. We found that the water extract of H. cordata leaves (WEH) inhibited the corn oil-induced increase in plasma triglyceride levels in mice. WEH also inhibited the oleic acid- and glycerol-induced increase in the levels of plasma nonesterified fatty acids and glycerol, respectively. Moreover, WEH had anti-obesity effects in mice with high-fat-diet-induced obesity. Therefore, WEH may be able to prevent or reduce obesity induced by a high-fat diet.

Antidiabetic Properties of Zinc-α2-Glycoprotein in ob/ob Mice

Zinc-alpha(2)-glycoprotein (ZAG) is an adipokine associated with fat loss in cancer cachexia. The purpose of this study was to evaluate the ability of recombinant human ZAG to attenuate type 2 diabetes in the ob/ob mouse model. ZAG (50 microg daily, iv) induced a progressive loss of body weight (3.5 g in 5 d), without an effect on food or water intake but with a 0.4 C rise in body temperature, suggesting an increased energy expenditure. Despite an increased plasma glycerol, indicative of increased lipolysis, levels of glucose, triglycerides, and nonesterified fatty acids were decreased by 17, 25, and 62%, respectively, due to an increased use of both glucose and lipids by muscle and brown adipose tissue. The weight of the latter increased 2-fold, and there was increased expression of uncoupling proteins-1 and -3. Plasma insulin levels were reduced by 36%, whereas pancreatic insulin was increased 4-fold, and there was a 53% decrease in the total area under the glucose curve in the glucose tolerance test and reduced insulin requirement. There was an increase in skeletal muscle mass due to an increase in protein synthesis and a decrease in protein degradation. These results suggest that ZAG may potentially be effective in the treatment of type 2 diabetes.

The effect of glycaemic index of high carbohydrate diets consumed over 5 days on exercise energy metabolism and running capacity in males

The aim of this study was to determine whether rates of total fat and carbohydrate oxidation and endurance capacity during running conducted in the fasted state are influenced by the glycaemic index (GI) of high carbohydrate diets consumed over 5 days. Nine healthy males performed three treadmill runs to exhaustion at 65% of maximum oxygen uptake ([Vdot]O2max): after a habitual diet (control trial), after 5 days on a high carbohydrate/high glycaemic index diet, and after 5 days on a high carbohydrate/low glycaemic index diet in randomized counterbalanced order. No significant differences in rates of fat and carbohydrate oxidation, concentrations of plasma insulin, glucose, non-esterified fatty acids and glycerol, or time to exhaustion were observed between the high carbohydrate/high glycaemic index and high carbohydrate/low glycaemic index trials. Compared with the control trial, the concentration of plasma glycerol and rate of fat oxidation were lower (P < 0.05) and the rate of carbohydrate oxidation higher (P < 0.05) in both the high carbohydrate/high glycaemic index diet and high carbohydrate/low glycaemic index trials during the run to exhaustion. In conclusion, the extent by which a high carbohydrate diet consumed over 5 days reduces rate of fat oxidation during subsequent running exercise in the fasted state is not influenced by the glycaemic index of the diet.

Lipid oxidation in overweight men after exercise and food intake

Fat oxidation (FO) is optimized during low- to moderate-intensity exercise in lean and obese subjects, whereas high-intensity exercise induces preferential FO during the recovery period. After food intake during the postexercise period, it is unknown if FO differs according to the intensity exercise in overweight subjects. Fat oxidation was thus evaluated in overweight men after low- and high-intensity exercise during the recovery period before and after food intake as well as during a control session. Ten healthy, sedentary, overweight men (age, 27.9 ± 5.6 years; body mass index, 27.8 ± 1.3 kg m −2; maximal oxygen consumption, 37 ± 3.9 mL min −1 kg −1) exercised on a cycloergometer (energy expenditure = 300 kcal) at 35% (E35) or 70% (E70) maximal oxygen consumption or rested (Cont). The subjects were fed 30 minutes after the exercise with 300 kcal (1256 kJ) more energy in the exercise sessions than in the Cont session. Respiratory quotient and FO were calculated by indirect calorimetry. Blood samples were analyzed to measure plasma glycerol, nonesterified fatty acid, glucose, and insulin. During exercise, mean respiratory quotient was lower ( P < .05) and FO was higher ( P < .01) in the E35 than in the E70 session (FO [in mg min −1]: E35 = 290 ± 12, E70 = 256 ± 38, and Cont = 131 ± 7). Conversely, FO was higher in the E70 than in both the E35 session and the Cont session during the immediate recovery as well as during the postprandial recovery period ( P = .005 for all; FO from the end of the exercise to the end of the session [in grams]: E70 = 45.7 ± 8.9, E35 = 38.2 ± 6.8, and Cont = 36.0 ± 4.3). Blood parameters did not differ between the 3 sessions but changed according to the absorption of the nutrients. In overweight subjects, high-intensity exercise increased FO during the postexercise period even after food intake compared with the low-intensity exercise and the control session.

Angiopoietin-like 4 (ANGPTL4, Fasting-induced Adipose Factor) Is a Direct Glucocorticoid Receptor Target and Participates in Glucocorticoid-regulated Triglyceride Metabolism

Glucocorticoids are important regulators of lipid homeostasis, and chronically elevated glucocorticoid levels induce hypertriglyceridemia, hepatic steatosis, and visceral obesity. The occupied glucocorticoid receptor (GR) is a transcription factor. However, those genes regulating lipid metabolism under GR control are not fully known. Angiopoietin-like 4 (ANGPTL4, fasting-induced adipose factor), a protein inhibitor of lipoprotein lipase, is synthesized and secreted during fasting, when circulating glucocorticoid levels are physiologically increased. We therefore tested whether the ANGPTL4 gene (Angptl4) is transcriptionally controlled by GR. We show that treatment with the synthetic glucocorticoid dexamethasone increased Angptl4 mRNA levels in primary hepatocytes and adipocytes (2-3-fold) and in the livers and white adipose tissue of mice (approximately 4-fold). We tested the mechanism of this increase in H4IIE hepatoma cells and found that dexamethasone treatment increased the transcriptional rate of Angptl4. Using bioinformatics and chromatin immunoprecipitation, we identified a GR binding site within the rat Angptl4 sequence. A reporter plasmid containing this site was markedly activated by dexamethasone, indicative of a functional glucocorticoid response element. Dexamethasone treatment also increased histone H4 acetylation and DNase I accessibility in genomic regions near this site, further supporting that it is a glucocorticoid response element. Glucocorticoids promote the flux of triglycerides from white adipose tissue to liver. We found that mice lacking ANGPTL4 (Angptl4(-/-)) had reductions in dexamethasone-induced hypertriglyceridemia and hepatic steatosis, suggesting that ANGPTL4 is required for this flux. Overall, we establish that ANGPTL4 is a direct GR target that participates in glucocorticoid-regulated triglyceride metabolism.