Serum Glycerol Concentrations Research Articles

Follistatin-like 1 is a myokine regulating lipid mobilization during endurance exercise and recovery.

The aim of this study was to investigate the role of the follistatin-like 1 (Fstl1) and disco-interacting protein 2 homolog A (DIP2a) axis in relation to lipid metabolism during and after endurance exercise and to elucidate the mechanisms underlying the metabolic effects of Fstl1 on adipocytes, considering its regulation by exercise and muscle mass and its link to obesity. Twenty-nine sedentary males participated in endurance exercise, and blood samples were collected during and after the exercise. Body composition, Fstl1, glycerol, epinephrine, growth hormone, and atrial natriuretic peptide were measured. 3T3-L1 adipocytes, with or without DIP2a knockdown, were treated with Fstl1 to assess glycerol release, cyclic AMP/cyclic GMP production, and hormone sensitive lipase phosphorylation. The association between DIP2a gene expression levels in human adipose tissues and exercise-induced lipolysis was examined. Fstl1 levels significantly increased during endurance exercise and following recovery, correlating with lean body mass and lipolysis. In 3T3-L1 adipocytes, Fstl1 increased glycerol release, cyclic GMP production, and hormone sensitive lipase activation, but these effects were attenuated by DIP2a knockdown. DIP2a gene expression in human adipose tissues correlated with serum glycerol concentrations during endurance exercise. Fstl1 is a myokine facilitating lipid mobilization during and after endurance exercise through DIP2a-mediated lipolytic effects in adipocytes.

Metabolic effects of training endurance horses in a field setting

Abstract Changes in serum biochemistry and skeletal muscle of horses in response to individual endurance rides of varying distance have been reported, as have the effects of submaximal treadmill training. This study evaluated the effects of a controlled field endurance training programme on energy metabolism. Five Arabian horses 6.8 ± 2.0 years (mean ± standard deviation) were trained for 16 weeks over progressively longer distances. The biceps femoris, triceps long head, and semitendinosus muscles were biopsied before and after 4-weekly runs of 10, 20 and 30 miles, respectively, and before and after 10, 20, 30 and 50 miles of a fourth run at the end of the training programme to measure 3-hydroxyacyl-CoA-dehydrogenase (HAD) and succinate dehydrogenase (SDH) activities and triglyceride (TG) and glycogen concentrations in those biopsies. Blood samples were obtained simultaneously to measure serum TG, free fatty acid (FFA), glycerol, glucagon, insulin, and cortisol concentrations. Data were analysed using RM-ANOVA for effects of training and distance. was considered significant. Training increased resting glycogen and TG concentrations in the biceps (, ), triceps (, ) and semitendinosus (, ), respectively. Both HAD and SDH activities increased in the biceps femoris (; ) and triceps (; ), respectively, but not in the semitendinosus. There was no training effect detected on serum hormone responses to exercise distance although serum glycerol (), glucagon () and cortisol () concentrations increased with increasing run distance, while insulin concentration decreased (). Glucagon and cortisol concentrations were correlated (r = 0.67; ). Serum TG decreased with exercise but at a slower rate following training, and serum FFA were higher during exercise following training when compared to the partially trained state. Overall, endurance training enhanced peripheral mobilisation of fat and its utilisation by working muscle, and resting muscle glycogen stores increased.

Ketone Monoester Ingestion Alters Metabolism and Simulated Rugby Performance in Professional Players

Ketone ingestion can alter metabolism but effects on exercise performance are unclear, particularly with regard to the impact on intermittent-intensity exercise and team-sport performance. Nine professional male rugby union players each completed two trials in a double-blind, randomized, crossover design. Participants ingested either 90 ± 9g carbohydrate (CHO; 9% solution) or an energy matched solution containing 20 ± 2g CHO (3% solution) and 590mg/kg body mass β-hydroxybutyrate monoester (CHO + BHB-ME) before and during a simulated rugby union-specific match-play protocol, including repeated high-intensity, sprint and power-based performance tests. Mean time to complete the sustained high-intensity performance tests was reduced by 0.33 ± 0.41s (2.1%) with CHO + BHB-ME (15.53 ± 0.52s) compared with CHO (15.86 ± 0.80s) placebo (p = .04). Mean time to complete the sprint and power-based performance tests were not different between trials. CHO + BHB-ME resulted in blood BHB concentrations that remained >2mmol/L during exercise (p < .001). Serum lactate and glycerol concentrations were lower after CHO + BHB-ME than CHO (p < .05). Coingestion of a BHB-ME with CHO can alter fuel metabolism (attenuate circulating lactate and glycerol concentrations) and may improve high-intensity running performance during a simulated rugby match-play protocol, without improving shorter duration sprint and power-based efforts.

Foetal hyperinsulinaemia and increased fat mass correlate negatively with circulating fatty acid concentrations in neonates of gestational diabetic mothers with dietary-controlled glycaemia.

Higher accretion of prenatal fat is associated with a higher proportion of obesity in children. However, most of the data on regulatory factors involved in fetal adipogenesis come from animal studies; in humans there is no evidence on how fetal insulin affects fatty acid concentrations and fetal adiposity. We evaluate the relationship between fetal adipose tissue accretion with insulin and fetal consumption of circulating fatty acid (FA). In fasting maternal blood at term and cord samples, from 41 gestational diabetes mellitus women (GDM) and 68 non-diabetic controls, serum compounds were determined. Individual FA were analyzed and expressed as concentrations of FA (mmol/L). Both groups had similar maternal serum glucose, insulin, triacylglycerol (TAG), non-esterified FA (NEFA), glycerol and leptin concentrations, but most individual maternal serum FA were lower in GDM than controls. Neonatal fat mass (FM) was higher in the GDM group even though neonatal birth weights were similar. In GDM cord serum glucose, insulin, NEFA and leptin were higher than controls, but glycerol and all individual FA were lower. In GDM neonates only, a negative correlation was found between each FA and FM, and there was a strong negative correlation between the concentrations of umbilical blood insulin and five major FA. Our results show for the first time that hyperinsulinemia in fetuses of GDM women increases FA utilization, which may contribute to to their increased adiposity.

Can offsetting the energetic cost of hibernation restore an active season phenotype in grizzly bears (Ursus arctos horribilis)?

Hibernation is characterized by depression of many physiological processes. To determine if this state is reversible in a non-food caching species, we fed hibernating grizzly bears (Ursus arctos horribilis) dextrose for 10 days to replace 53% or 100% of the estimated minimum daily energetic cost of hibernation. Feeding caused serum concentrations of glycerol and ketones (β-hydroxybutyrate) to return to active season levels irrespective of the amount of glucose fed. By contrast, free fatty acids (FFAs) and indices of metabolic rate, such as general activity, heart rate, strength of heart rate circadian rhythm, and insulin sensitivity were restored to approximately 50% of active season levels. Body temperature was unaffected by feeding. To determine the contribution of adipose to the metabolic effects observed after glucose feeding, we cultured bear adipocytes collected at the beginning and end of the feeding and performed metabolic flux analysis. We found a ∼33% increase in energy metabolism after feeding. Moreover, basal metabolism before feeding was 40% lower in hibernation cells compared with fed cells or active cells cultured at 37°C, thereby confirming the temperature independence of metabolic rate. The partial depression of circulating FFAs with feeding likely explains the incomplete restoration of insulin sensitivity and other metabolic parameters in hibernating bears. Further depression of metabolic function is likely to be an active process. Together, the results provide a highly controlled model to examine the relationship between nutrient availability and metabolism on the hibernation phenotype in bears.

Virilizing doses of testosterone decrease circulating insulin levels and differentially regulate insulin signaling in liver and adipose tissue of females.

Transgender men undergoing hormone therapy are at risk for insulin resistance. However, how virilizing testosterone therapy affects serum insulin and peripheral insulin sensitivity in transgender men is unknown. This study assessed the effect of acute, virilizing testosterone on serum insulin concentrations and insulin signaling in liver, skeletal muscle, and white adipose tissue (WAT) of female pigs as a translational model for transgender men. Females received three doses of intramuscular testosterone cypionate (TEST females; 50 mg/day/pig) or corn oil (control) spaced 6 days apart starting on the day of estrus (D0). Fasting blood was collected on D0, D3, D5, D11, and D13, and females were euthanized on D13. On D13, TEST females had virilizing concentrations of serum testosterone with normal concentrations of serum estradiol. Virilizing serum testosterone concentrations (D13) were associated with decreased serum insulin and C-peptide concentrations. Blood glucose and serum glycerol concentrations were not altered by testosterone. Virilizing concentrations of testosterone downregulated AR and ESR1 in subcutaneous (sc) WAT and upregulated transcript levels of insulin-signaling pathway components in WAT and liver. At the protein level, virilizing testosterone concentrations were associated with increased PI3K 110α in liver and increased insulin receptor (INSR) and phospho(Ser256)-FOXO1 in visceral (v) WAT but decreased phospho(Ser473)-AKT in vWAT and scWAT. These results suggest that acute exposure to virilizing concentrations of testosterone suppresses circulating insulin levels and results in increased abundance of proteins in the insulin-signaling pathway in liver and altered phosphorylation of key proteins in control of insulin sensitivity in WAT.NEW & NOTEWORTHY Acute virilizing doses of testosterone administered to females suppress circulating insulin levels, upregulate components of the insulin-signaling pathway in liver, and suppress insulin signaling in white adipose tissue. These results suggest that insulin resistance in transgender men may be due to suppression of the insulin-signaling pathway and decreased insulin sensitivity in white adipose tissue.

The acute effects of thermogenic fitness drink formulas containing 140\u2009mg and 100\u2009mg of caffeine on energy expenditure and fat metabolism at rest and during exercise

BackgroundThermogenic fitness drink formulas (TFD) have been shown to increase energy expenditure and markers of lipid metabolism. The purpose of the current study was to compare TFD formulas containing different caffeine concentrations versus a placebo drink on energy expenditure and lipid metabolism at rest and during exercise.MethodsThirty-two recreationally active participants (22.9 ± 0.7 y, 167.1 ± 1.4 cm, 68.8 ± 2.0 kg, 24.0 ± 1.2% fat) who were regular caffeine consumers, participated in this randomized, double-blind, crossover design study. Participants reported to the laboratory on three occasions, each of which required consumption of either a TFD containing 140 mg or 100 mg of caffeine or a placebo. Baseline measurements of resting energy expenditure (REE) and resting fat oxidation (RFO) were assessed using indirect calorimetry as well as measurements of serum glycerol concentration. Measurements were repeated at 30, 60, 90 min post-ingestion. Following resting measures, participants completed a graded exercise test to determine maximal oxygen uptake (V̇O2max), maximal fat oxidation (MFO) and the exercise intensity that elicits MFO (Fatmax), and total energy expenditure (EE).ResultsA significant interaction was shown for REE (p < 0.01) and RFO (p < 0.01). Area under the curve analysis showed an increased REE for the 140 mg compared to the 100 mg formula (p = 0.02) and placebo (p < 0.01) and an increased REE for the 100 mg formula compared to placebo (p = 0.02). RFO significantly decreased for caffeinated formulas at 30 min post ingestion compared to placebo and baseline (p < 0.01) and significantly increased for the 140 mg formula at 60 min post-ingestion (p = 0.03). A main effect was shown for serum glycerol concentrations over time (p < 0.01). No significant differences were shown for V̇O2max (p = 0.12), Fatmax (p = 0.22), and MFO (p = 0.05), and EE (p = 0.08) across drinks.ConclusionsOur results suggest that TFD formulas containing 100 and 140 mg of caffeine are effective in increasing REE and that a 40 mg of caffeine difference between the tested formulas may impact REE and RFO in healthy individuals within 60 min of ingestion.

Fasting reveals largely intact systemic lipid mobilization mechanisms in respiratory chain complex III deficient mice

Mice homozygous for the human GRACILE syndrome mutation (Bcs1lc.A232G) display decreased respiratory chain complex III activity, liver dysfunction, hypoglycemia, rapid loss of white adipose tissue and early death. To assess the underlying mechanism of the lipodystrophy in homozygous mice (Bcs1lp.S78G), these and wild-type control mice were subjected to a short 4-hour fast. The homozygotes had low baseline blood glucose values, but a similar decrease in response to fasting as in wild-type mice, resulting in hypoglycemia in the majority. Despite the already depleted glycogen and increased triacylglycerol content in the mutant livers, the mice responded to fasting by further depletion and increase, respectively. Increased plasma free fatty acids (FAs) upon fasting suggested normal capacity for mobilization of lipids from white adipose tissue into circulation. Strikingly, however, serum glycerol concentration was not increased concomitantly with free FAs, suggesting its rapid uptake into the liver and utilization for fuel or gluconeogenesis in the mutants. The mutant hepatocyte mitochondria were capable of responding to fasting by appropriate morphological changes, as analyzed by electron microscopy, and by increasing respiration. Mutants showed increased hepatic gene expression of major metabolic controllers typically associated with fasting response (Ppargc1a, Fgf21, Cd36) already in the fed state, suggesting a chronic starvation-like metabolic condition. Despite this, the mutant mice responded largely normally to fasting by increasing hepatic respiration and switching to FA utilization, indicating that the mechanisms driving these adaptations are not compromised by the CIII dysfunction. Summary statementBcs1l mutant mice with severe CIII deficiency, energy deprivation and post-weaning lipolysis respond to fasting similarly to wild-type mice, suggesting largely normal systemic lipid mobilization and utilization mechanisms.

Effect Of Wearing Compression Tights On Muscle Oxygenation And Exogenous Glucose Utilization During Prolonged Cycling

PURPOSE: To determine effect of wearing compression tights on muscle oxygenation and exogenous glucose utilization during prolonged cycling in endurance athletes. METHODS: Ten triathletes (19.9 ± 1.2 years, 172.2 ± 4.4 cm, 62.0 ± 3.8 kg,BMI; 20.9 ± 0.7 kg·m-2; VO2max; 59.3 ± 4.4 ml·kg -1·min -1) completed 3 trials under respective conditions: 1) wearing a compression tight with approximately 15 mmHg [MED trial], 2) wearing a compression tight with approximately 30 mmHg [HIGH trial], and 3) wearing a tight with below 5 mmHg [CON trial]. The exercise consisted of 90 min of cycling at 65% of VO2max. Changes in exogenous glucose utilization (13C excretion in expired gas after consuming 13C labeled glucose), muscle oxygenation (oxy-hemoglobin, deoxy-hemoglobin, total hemoglobin and tissue saturation index), blood parameters (blood glucose and lactate, and serum glycerol, insulin and total ketone body concentrations), blood gas parameters (pH, pO2, pCO2, HCO3-, Na+ and K+), respiratory variables (VO2, VCO2, VE, RER), heart rate and rating of perceived exertion were evaluated throughout the exercise. Time to exhaustion test (at 85% of VO2max) was performed after completing 90 min of cycling to evaluate endurance performance. RESULTS: Exercise rapidly increased 13C excretion, but highest value of 13C excretion was significantly shown earlier in the MED trial (47.1 ± 9.9 min) compared with in the other trials (HIGH trial: 67.3 ± 23.7 min, CON trial: 54.0 ± 9.5 min, P = 0.033). Although MED trial showed significant lower oxy-hemoglobin throughout the exercise (P = 0.003), the changes in deoxy-hemoglobin, total hemoglobin and tissue oxygenation index did not differ among the trials. No significant difference was observed for changes in other variables among the trials. CONCLUSION: Wearing a compression tights exerting approximately 15 mmHg on thigh facilitated exogenous glucose utilization during 90 min of cycling.

Reproduction of contagious caprine pleuropneumonia reveals the ability of convalescent sera to reduce hydrogen peroxide production in vitro

Contagious caprine pleuropneumonia (CCPP), caused by Mycoplasma capricolum subsp. capripneumoniae is a severe disease widespread in Africa and Asia. Limited knowledge is available on the pathogenesis of this organism, mainly due to the lack of a robust in vivo challenge model and the means to do site-directed mutagenesis. This work describes the establishment of a novel caprine challenge model for CCPP that resulted in 100% morbidity using a combination of repeated intranasal spray infection followed by a single transtracheal infection employing the recent Kenyan outbreak strain ILRI181. Diseased animals displayed CCPP-related pathology and the bacteria could subsequently be isolated from pleural exudates and lung tissues in concentrations of up to 109 bacteria per mL as well as in the trachea using immunohistochemistry. Reannotation of the genome sequence of ILRI181 and F38T revealed the existence of genes encoding the complete glycerol uptake and metabolic pathways involved in hydrogen peroxide (H2O2) production in the phylogenetically related pathogen M. mycoides subsp. mycoides. Furthermore, the expression of L-α-glycerophosphate oxidase (GlpO) in vivo was confirmed. In addition, the function of the glycerol metabolism was verified by measurement of production of H2O2 in medium containing physiological serum concentrations of glycerol. Peroxide production could be inhibited with serum from convalescent animals. These results will pave the way for a better understanding of host–pathogen interactions during CCPP and subsequent vaccine development.

Performance, meat quality and fatty acid profile of broiler chickens fed mixed semi-purified glycerin

The aim of the present study was to evaluate the effects of the inclusion of mixed (animal and vegetable sources) semi-purified glycerin (MSPG) in broiler diets on performance, litter moisture, serum glycerol concentration, carcass and parts yields, meat quality, and the fatty acid profile. In total, 576 1-day-old male Cobb 500 broiler chicks were distributed in a completely randomised design into four treatments (0%, 2.5%, 5.0% and 7.5% dietary inclusion levels of MSPG, as-fed basis), with six replicate pens of 24 birds each. The apparent metabolisable energy corrected for nitrogen balance and energy metabolisability coefficient values of the MSPG were 12.33 MJ/kg DM and 81.61% respectively. There was no significant (P &amp;gt; 0.05) effect of the MSPG concentration on the performance, and carcass and parts yields or broiler meat-quality variables, except for thigh meat colour, in which the yellowness value (b*) decreased linearly (P &amp;lt; 0.05) with an increasing inclusion level of MSPG. Litter moisture and serum glycerol increased linearly (P &amp;lt; 0.05) and the lipid profile of the thigh and drumstick meat of broilers at 42 days of age was slightly altered (P &amp;lt; 0.05) with an increasing MSPG. Mixed semi-purified glycerin can be used at up to 7.5% in broiler diets without impairing performance, meat quality, carcass and parts yields from 1 to 42 days of age. However, special attention should be paid to litter moisture.

Molecular Cloning of cDNA Encoding an Aquaglyceroporin, AQP-h9, in the Japanese Tree Frog, Hyla japonica: Possible Roles of AQP-h9 in Freeze Tolerance.

In order to study the freeze-tolerance mechanism in the Japanese tree frog, Hyla japonica, wecloned a eDNA encoding aquaporin (AQP) 9 from its liver. The predicted amino acid sequence ofH. japonica AQP9 (AQP-h9) contained six putative transmembrane domains and two conservedAsn-Pro-Aia motifs, which are characteristic of AQPs. A swelling assay using Xenopus laevisoocytes injected with AQP-h9 cRNA showed that AQP-h9 facilitated water and glycerol permeation,confirming its property as an aquaglyceroporin. Subsequently, glycerol concentrations in serumand tissue extracts were compared among tree frogs that were hibernating, frozen, or thawed afterfreezing. Serum glycerol concentration of thawed frogs was significantly higher than that of hibernatingfrogs. Glycerol content in the liver did not change in the freezing experiment, whereas thatin the skeletal muscle was elevated in thawed frogs as compared with hibernating or frozen frogs. Histological examination of the liver showed that erythrocytes aggregated in the sinusoids during hibernation and freezing, and immunoreactive AQP-h9 protein was detected over the erythrocytes. The AQP-h9 labeling was more intense in frozen frogs than in hibernating frogs, but nearly undetectable in thawed frogs. For the skeletal muscle, weak labels for AQP-h9 were observed in the cytoplasm of myocytes of hibernating frogs. AQP-h9 labeling was markedly enhanced by freezing and was decreased by thawing. These results indicate that glycerol may act as a c;:ryoprotectant in H. japonica and that during hibernation, particularly during freezing, AQP-h9 may be involved in glycerol uptake in erythrocytes in the liver and in intracellular glycerol transport in the skeletal muscle cells.

Augmented Carbohydrate Oxidation under Moderate Hypobaric Hypoxia Equivalent to Simulated Altitude of 2500 m

Hypoxia itself stimulates glucose uptake mediated by a mechanism independent of insulin. However, whether moderate hypoxia causes similar metabolic effect in humans remains unclear. The present study aimed to determine glycemic regulation following glucose load at a simulated moderate altitude of 2,500 m. Eight healthy young males (mean ± standard error: 24 ± 1 years; 171.3 ± 1.6 cm; 66.9 ± 3.7 kg; 22.8 ± 1.0 kg/m(2)) consumed 75 g of glucose solution under either hypobaric condition (560 mmHg) or normobaric condition (745 mmHg). In the hypobaric chamber, the oxygen partial pressure is proportionally reduced with a reduction of atmospheric pressure, consequently leading to the hypoxic condition. Plasma glucose and serum insulin concentrations increased significantly following glucose load in both conditions (P < 0.05). However, no significant interaction (condition × time) or main effect for condition was observed. There were no significant differences in serum glycerol, plasma epinephrine, or plasma norepinephrine concentrations between the two conditions. No significant differences between the conditions were observed in changes in VO2 or VCO2. However, the hypobaric condition showed significantly higher respiratory exchange ratio (VCO2/VO2) at 90 and 120 min following glucose load (P < 0.05 vs. normobaric condition), suggesting that carbohydrate oxidation following glucose load was enhanced in moderate hypobaric hypoxia. In conclusion, acute exposure to moderate hypobaric hypoxia significantly augmented carbohydrate oxidation following the glucose load, without affecting glucose or insulin responses. Thus, a short-time exposure to moderate hypobaric hypoxia may be beneficial for people with impaired glucose tolerance.

Fuel selection during short-term submaximal treadmill exercise in the cold is not affected by pre-exercise low-intensity shivering

Exercise and shivering rely on different metabolic pathways and consequently, fuel selection. The present study examined the effects of a pre-exercise low-intensity shivering protocol on fuel selection during submaximal exercise in a cold environment. Nine male subjects exercised 4 times for 60 min at 50% (LOW) or 70% (MOD) of their peak oxygen consumption on a motorized treadmill in a climatic chamber set at 0 °C with (SHIV) and without (CON) a pre-exercise cooling protocol, inducing low-intensity shivering. Thermal, cardiorespiratory and metabolic responses were measured every 15 min whereas blood samples were collected every 30 min to assess serum nonesterified fatty acids (NEFA), glycerol, glucose, β-hydroxybutyrate (BHB) and plasma catecholamine concentrations. Rectal and skin temperatures were lower in the SHIV condition, within LOW and MOD conditions, during the first 45 min of exercise. Norepinephrine (NE) concentration was greater in SHIV vs. CON within LOW (1.39 ± 0.17 vs. 0.98 ± 0.17 ng·mL(-1)) and MOD (1.50 ± 0.20 vs. 1.01 ± 0.09 ng·mL(-1)), whereas NEFA, glycerol and BHB were greater in SHIV vs. CON (1060 ± 49 vs. 898 ± 78 μmol·L(-1); 0.27 ± 0.02 vs. 0.22 ± 0.03 mmol·L(-1); 0.39 ± 0.06 vs. 0.27 ± 0.04 mmol·L(-1), respectively) within MOD only. No changes were observed in fat or carbohydrate oxidation between SHIV and CON during exercise. Despite increases in NE, NEFA, glycerol and BHB from pre-exercise low-intensity shivering, fuel selection during short-term submaximal exercise in the cold was unaltered.

Serum triglycerides and ß-hydroxybutyrate predict feeding status in green turtles (Chelonia mydas): Evaluating a single blood sample method for assessing feeding/fasting in reptiles

The foraging success or feeding rate of an animal is important information for ecologists and wildlife managers but can be difficult to assess, particularly in marine vertebrates that are hard to follow at sea. Here we evaluate a method for determining recent feeding history using a single blood sample by measuring the concentration of relevant serum metabolites. Five captive green turtles were either fed a maintenance diet or subjected to fasting periods ranging from 5–15days. Serial serum samples were collected during both fed and fasted periods, and we determined triglyceride, ß-hydroxybutyrate, and glycerol concentrations using spectrophotometric assays. Serum triglyceride and glycerol concentrations decreased during fasting periods, while serum ß-hydroxybutyrate concentration increased during fasts. For triglyceride and glycerol, this decrease apparently occurred in the first 5days of fasting and was unaltered by further fasting. ß-hydroxybutyrate concentration continued to increase during longer fasting periods. The decrease in serum glycerol was unexpected and may be due to metabolic down-regulation in fasted turtles. Serum triglyceride and ß-hydroxybutyrate appear to be good indicators of feeding state and can be applied to wild turtles.

The Calcium-Sensing Receptor Affects Fat Accumulation via Effects on Antilipolytic Pathways in Adipose Tissue of Rats Fed Low-Calcium Diets

Low-calcium intake is associated with increased risk of obesity, but the mechanism underlying this is not clear. We previously reported that the calcium-sensing receptor (CaSR) plays an important role in modulating the expression of rate-limiting lipolysis enzymes in human adipocytes. In the present study, rats were fed diets containing normal [0.50% (NC)], low [0.30% (LC)], or very low [0.15% (VLC)] calcium for 15 wk. Ten rats of each group were killed at wk 5, 10, and 15 of the intervention. The LC-fed rats had greater visceral fat mass, lower serum FFA and glycerol concentrations, and greater CaSR expression in white adipose tissue than did those fed the NC diet at wk 10 and 15. Hormone-sensitive lipase (HSL) and adipose TG lipase (ATGL) protein levels were lower, whereas fatty acid synthase mRNA in white adipose tissue was greater in the LC-fed rats compared with the NC-fed rats. These differences from the NC group were greater in the VLC group than in the LC group at wk 15. In vitro experiments showed that 1,25-dihydroxycholecalciferol stimulated the expression of CaSR through the nuclear vitamin D receptor (nVDR). This resulted in an antilipolytic effect by increasing intracellular calcium, decreasing the intracellular cAMP level, and downregulating HSL and ATGL protein expression in adipocytes. These effects were suppressed by either nVDR or CaSR small-interfering RNA. These results suggest that CaSR affects fat accumulation by mediating antilipolytic pathways in adipose tissue of rats fed low-calcium diets.

Metabolic Alterations in Adipose Tissue During the Early Phase of Experimental Endotoxemia in Humans

Adipose tissue plays an important role in energy homeostasis; however, there is only little knowledge about its metabolic activity during critical illness or sepsis. We assessed adipose tissue metabolic activity and local blood flow during experimental endotoxemia in otherwise healthy humans. In a prospective, placebo controlled and randomized experiment we measured changes in lactate, glycerol, and pyruvate concentrations in microdialysate samples of femoral adipose tissue after an intravenous bolus of lipopolysaccharide (LPS, 4 ng/kg). Intravenous endotoxin caused an early and constant increase in interstitial pyruvate, while formation of lactate in adipose tissue was not affected. In contrast, lactate levels in serum were elevated significantly after 90 min (p<0.05) and likewise, serum glycerol concentrations rose 90 min after LPS treatment (p<0.05) and 60 min earlier than in adipose tissue. Subcutaneous adipose tissue blood perfusion increased 2-fold while there was a strong decline in skin blood flow. Pyruvate accumulation in subcutaneous adipose tissue is an early marker of endotoxemia. While adipose tissue is a major source of serum glycerol and lactate in humans during physiological conditions, it contributes only little to increased serum lactate and glycerol levels during endotoxemia.

Glycerol homeostasis and metabolism in glycerol kinase carrier mice

To examine glycerol homeostasis and metabolism is essential for understanding of pathogenesis and evaluation of treatment efficacy in disorders of glycerol metabolism. In this study, we designed the intraperitoneal glycerol tolerance test (IPGlyTT) and studied glycerol tolerance in vivo using glycerol kinase (Gyk) carrier (C) and wild type (WT) mice. Serum glycerol concentrations in WT almost normalized at 90 min after injection, whereas Gyk C mice retained high serum glycerol concentrations at least until 180 min after injection. These results showed that glycerol tolerance was impaired in Gyk C mice compared to WT mice. The IPGlyTT is useful in accessing glycerol homeostasis and metabolism in animal models such as Gyk C mice and will be valuable in assessing therapeutic interventions in Gyk KO mice.

Evaluation of the nutritional value of glycerol for nursery pigs1

In Exp. 1, a total of 144 pigs (BW, 6.68 ± 0.17 kg) were weaned at 21 d, blocked by BW, and allocated to 48 pens with 3 pigs per pen. Pens were randomly assigned to 1 of 6 dietary treatments (0, 2.5, 5, 7.5, and 10% glycerol supplemented to replace up to 10% lactose in a basal starter 1 diet containing 20% total lactose, which was fed for 2 wk), and a negative control diet with 10% lactose and 0% glycerol. A common starter diet was fed for the next 2 wk. In Exp. 2, a total of 126 pigs (BW, 6.91 ± 0.18 kg) were weaned at 21 d of age, blocked by BW, and allocated to 42 pens with 3 pigs per pen. Pigs were assigned to 1 of 6 treatments in a 2 × 3 factorial arrangement in a randomized complete block design with factors being 1) glycerol inclusion in replacement of lactose in starter 1 diets (0 or 5%) fed for 2 wk, and 2) glycerol inclusion in starter 2 diets (0, 5, or 10%) fed for 3 wk. In Exp. 1, glycerol supplementation at 10% improved (P=0.01) ADG (266 vs. 191 g/d) and G:F (871 vs. 679 g/kg) during the starter 1 period when compared with the negative control. Incremental amounts of glycerol linearly (P<0.05) increased ADG and ADFI, but did not affect G:F during starter 1. There was no effect of feeding glycerol during the starter 1 phase on subsequent performance during the starter 2 phase or overall. Serum glycerol concentrations increased linearly (P=0.003) with increasing dietary glycerol, and serum creatinine (P=0.004) and bilirubin (P=0.03) concentrations decreased with increasing glycerol. In Exp. 2, glycerol did not affect performance during starter 1, but it linearly increased (P≤0.01) ADG and ADFI during starter 2 (464, 509, and 542 and 726, 822, and 832 g/d, respectively) and overall (368, 396, and 411 and 546, 601, and 609 g/d, respectively). At the end of the study, pigs were 1.0 and 1.5 kg heavier when fed 5 and 10% glycerol, respectively (linear, P<0.01). Serum glycerol concentrations increased linearly during starter 2 (P<0.001), but were not affected during starter 1. Glycerol supplementation increased serum urea N quadratically (P<0.001) and decreased creatinine linearly (P<0.05) in the starter 2 phase. Overall, data indicate that glycerol can be added to nursery pig diets at 10%, while improving growth performance.

Apelin Decreases Lipolysis via Gq, Gi, and AMPK-Dependent Mechanisms

The release of free fatty acids (FFAs) from adipocytes (i.e. lipolysis) is increased in obesity and is a contributory factor to the development of insulin resistance. A recently identified adipokine, apelin, is up-regulated in states of obesity. Although apelin is secreted by adipocytes, its functions in them remain largely unknown. To determine whether apelin affects lipolysis, FFA, glycerol, and leptin levels, as well as abdominal adiposity, were measured at baseline and after reintroduction of exogenous apelin in apelin-null mice. To examine apelin's effects in vitro, isoproterenol-induced FFA/glycerol release, and hormone-sensitive lipase (HSL) and acetyl CoA carboxylase phosphorylation were investigated in 3T3-L1 cells and isolated wild-type adipocytes. Serum FFA, glycerol, and leptin concentrations, as well as abdominal adiposity, were significantly increased in apelin-null vs. wild-type mice; these changes were ameliorated in response to exogenous apelin. Apelin also reduced isoproterenol-induced FFA release in adipocytes isolated from wild-type but not APJ-null mice. In 3T3-L1 cells and isolated adipocytes, apelin attenuated isoproterenol-induced FFA/glycerol release. Apelin's inhibition was reversed by pertussis toxin, the G(q) inhibitor glycoprotein antagonist 2A, and the AMP-activated protein kinase inhibitors compound C and dorsomorphin. Apelin increased HSL phosphorylation at Ser-565 and also abrogated isoproterenol-induced HSL phosphorylation at Ser-563. Notably, apelin increased acetyl CoA carboxylase phosphorylation, suggesting AMPK activation. In conclusion, apelin negatively regulates lipolysis. Its actions may be mediated by pathways involving G(q), G(i), and AMP-activated protein kinase.