Plasma Glycerol Concentrations Research Articles

Acute Statin Withdrawal Does not Interfere With the Improvements of a Session of Exercise in Postprandial Metabolism.

The risk for atherogenic plaque formation is high after ingestion of meals in individuals with high blood lipid levels (ie, dyslipidemia). Statins and exercise reduce the rise of blood triglyceride concentrations after a meal, but the effect of their combination is unclear. In a randomized crossover design, 11 individuals with dyslipidemia and metabolic syndrome treated with statins underwent a mixed-meal (970 ± 111 kcal, 24% fat, and 34% carbohydrate) tolerance test. Plasma lipid concentrations, fat oxidation, glucose, and glycerol kinetics were monitored immediately prior and during the meal test. Trials were conducted with participants under their habitual statin treatment and 96 hours after blinded statin withdrawal. Trials were duplicated after a prolonged bout of low-intensity exercise (75 minutes at 53 ± 4% maximal oxygen consumption) to study the interactions between exercise and statins. Statins reduced postprandial plasma triglycerides from 3.03 ± 0.85 to 2.52 ± 0.86 mmol·L-1 (17%; P = .015) and plasma glycerol concentrations (ie, surrogate of whole-body lipolysis) without reducing plasma free fatty acid concentration or fat oxidation. Prior exercise increased postprandial plasma glycerol levels (P = .029) and fat oxidation rates (P = .024). Exercise decreased postprandial plasma insulin levels (241 ± 116 vs 301 ± 172 ρmol·L-1; P = .026) but not enough to increase insulin sensitivity (P = .614). Neither statins nor exercise affected plasma glucose appearance rates from exogenous or endogenous sources. In dyslipidemic individuals, statins reduce blood triglyceride concentrations after a meal, but without limiting fat oxidation. Statins do not interfere with exercise lowering the postprandial insulin that likely promotes fat oxidation. Last, statins do not restrict the rates of plasma incorporation or oxidation of the ingested glucose.

The effect of varying concentrations of chicken plasma egg yolk and glycerol on the viability of canine sperm following short and long-term preservation.

Plasma egg yolk (PEY), due to simple preparation and easier access, could be a suitable alternative to raw egg yolk for preserving canine semen. The present study investigated suitable concentrations of PEY and glycerol for preservation of canine semen. Semen was collected by digital manipulation (seven replicates from four dogs). Following initial raw semen evaluation, the semen was diluted in a tris-based extender supplemented with varying concentrations of chicken PEY (0, 20, and 40% v/v) and glycerol (3%; v/v). After cooling the specimen to 4°C within 1 h, the specimens were diluted with an equal volume of freezing extender consisting of similar concentrations of chicken PEY and 0 and 7% glycerol to reach the final glycerol concentration of 1.5 and 5% for short-term storage of canine semen. Samples with different concentrations of PEY and 5% glycerol were frozen. The sperm viability parameters including total motility, progressive forward motility, plasma membrane integrity, and live percentage of sperm were assessed following short and long-term storage. Sperm viability parameters of semen extended in an extender supplemented with 20 or 40% chicken PEY with either 1.5 or 5% glycerol remained superior until 72 h after semen collection compared to the specimen that did not receive any PEY (P<0.05). Post-thaw sperm viability was also greater in samples extended in extender supplemented with either 20 or 40% PEY compared to 0% PEY. Tris-based extender supplemented with either 20% chicken PEY could be suitable for short and long-term preservation of canine semen.

High-fat diet changes the behavioural and hormonal responses to water deprivation in male Wistar rats.

What is the central question of this study? What is the effect of an obesogenic diet on the control of hydromineral balance in rats? What is the main finding and its importance? The results showed that, when dehydrated, rats fed a high-fat diet drink less water than their control-diet-fed counterparts. Changes in aquaporin-7 and peroxisome proliferator-activated receptor α expression in the white adipose tissue might be involved. High-fat diet (HFD) increases fat accumulation, glycaemia and blood triglycerides and is used as a model to study obesity. Besides the metabolic changes, obesity likely affects water intake. We assessed the effects of HFD on behavioural and hormonal responses to water deprivation. Additionally, we measured if the adipose tissue is differentially affected by water deprivation in control and HFD-fed rats. HFD rats showed a decreased basal water intake when compared to control-fed rats. When subjected to 48h of water deprivation, as expected, both control and HFD rats drank more water than the hydrated rats. However, the increase in water intake was lessened in HFD dehydrated rats. Similarly, the increase in haematocrit in dehydrated rats was less pronounced in HFD dehydrated rats. These results suggest that HFD diminishes drinking behaviour. White adipose tissue weight, glycaemia and plasma glycerol concentration were increased in HFD rats; however, after 48h of water deprivation, these parameters were significantly decreased in dehydrated HFD rats, when compared to controls. The increase in adipose tissue caused by HFD may mitigate the effects of dehydration, possibly through the increased production of metabolic water caused by lipolysis in the adipocytes. Oxytocin possibly mediates the lipolytic response, since both its secretion and receptor expression are affected by dehydration in both control and HFD rats, which suggests that oxytocin signalling is maintained in these conditions. Changes in mediators of lipolysis, such as aquaporin-7 and peroxisome proliferator-activated receptor α, might contribute to the different effects observed in control and HFD rats.

Mathematical modeling reveals differential dynamics of insulin action models on glycerol and glucose in adolescent girls with obesity.

Under healthy conditions, the pancreas responds to a glucose challenge by releasing insulin. Insulin suppresses lipolysis in adipose tissue, thereby decreasing plasma glycerol concentration, and it regulates plasma glucose concentration through action in muscle and liver. Insulin resistance (IR) occurs when more insulin is required to achieve the same effects, and IR may be tissue-specific. IR emerges during puberty as a result of high concentrations of growth hormone and is worsened by youth-onset obesity. Adipose, liver, and muscle tissue exhibit distinct dose-dependent responses to insulin in multi-phase hyperinsulinemic-euglycemic (HE) clamps, but the HE clamp protocol does not address potential differences in the dynamics of tissue-specific insulin responses. Changes to the dynamics of insulin responses would alter glycemic control in response to a glucose challenge. To investigate the dynamics of insulin acting on adipose tissue, we developed a novel differential-equations based model that describes the coupled dynamics of glycerol concentrations and insulin action during an oral glucose tolerance test in female adolescents with obesity and IR. We compared these dynamics to the dynamics of insulin acting on muscle and liver as assessed with the oral minimal model applied to glucose and insulin data collected under the same protocol. We found that the action of insulin on glycerol peaks approximately 67 min earlier (p < 0.001) and follows the dynamics of plasma insulin more closely compared to insulin action on glucose as assessed by the parameters representing the time constants for insulin action on glucose and glycerol (p < 0.001). These findings suggest that the dynamics of insulin action show tissue-specific differences in our IR adolescent population, with adipose tissue responding to insulin more quickly compared to muscle and liver. Improved understanding of the tissue-specific dynamics of insulin action may provide novel insights into the progression of metabolic disease in patient populations with diverse metabolic phenotypes.

Thermogenesis is supported by high rates of circulatory fatty acid and triglyceride delivery in highland deer mice.

Highland native deer mice (Peromyscus maniculatus) have greater rates of lipid oxidation during maximal cold challenge in hypoxia (hypoxic cold-induced V̇O2,max) compared with their lowland conspecifics. Lipid oxidation is also increased in deer mice acclimated to simulated high altitude (cold hypoxia), regardless of altitude ancestry. The underlying lipid metabolic pathway traits responsible for sustaining maximal thermogenic demand in deer mice is currently unknown. The objective of this study was to characterize key steps in the lipid oxidation pathway in highland and lowland deer mice acclimated to control (23°C, 21 kPa O2) or cold hypoxic (5°C, 12 kPa O2) conditions. We hypothesized that capacities for lipid delivery and tissue uptake will be greater in highlanders and further increase with cold hypoxia acclimation. With the transition from rest to hypoxic cold-induced V̇O2,max, both highland and lowland deer mice showed increased plasma glycerol concentrations and fatty acid availability. Interestingly, acclimation to cold hypoxia led to increased plasma triglyceride concentrations at cold-induced V̇O2,max, but only in highlanders. Highlanders also had significantly greater delivery rates of circulatory free fatty acids and triglycerides due to higher plasma flow rates at cold-induced V̇O2,max. We found no population or acclimation differences in fatty acid translocase (FAT/CD36) abundance in the gastrocnemius or brown adipose tissue, suggesting that fatty acid uptake across membranes is not limiting during thermogenesis. Our data indicate that circulatory lipid delivery plays a major role in supporting the high thermogenic rates observed in highland versus lowland deer mice.

Effect of Exogenous Hydrogen Sulfide and Polysulfide Donors on Insulin Sensitivity of the Adipose Tissue.

Hydrogen sulfide (H2S) and inorganic polysulfides are important signaling molecules; however, little is known about their role in adipose tissue. We examined the effect of H2S and polysulfides on insulin sensitivity of the adipose tissue in rats. Plasma glucose, insulin, non-esterified fatty acids, and glycerol were measured after administration of H2S and the polysulfide donors, Na2S and Na2S4, respectively. In addition, the effect of Na2S and Na2S4 on insulin-induced glucose uptake and inhibition of lipolysis was studied in adipose tissue explants ex vivo. Na2S and Na2S4 administered in vivo at a single dose of 100 μmol/kg had no effect on plasma glucose and insulin concentrations. In addition, Na2S and Na2S4 did not modify the effect of insulin on plasma glucose, fatty acids, and glycerol concentrations. Na2S and Na2S4had no effect on the antilipolytic effect of insulin in adipose tissue explants ex vivo. The effect of insulin on 2-deoxyglucose uptake by adipose tissue was impaired in obese rats which was accompanied by lower insulin-induced tyrosine phosphorylation of IRS-1 and Akt. Na2S4, but not Na2S, improved insulin signaling and increased insulin-stimulated 2-deoxyglucose uptake by adipose tissue of obese rats. The results suggest that polysulfides may normalize insulin sensitivity, at least in the adipose tissue, in obesity/metabolic syndrome.

Cholecystokinin promotes functional expression of the aquaglycerol channel aquaporin 7 in adipocytes.

Cholecystokinin (CCK) promotes triglyceride storage and adiponectin production in white adipose tissue (WAT), suggesting that CCK modulates WAT homeostasis. Our goal was to investigate the role of CCK in regulating the expression and function of the aquaglycerol channel aquaporin 7 (AQP7), a protein that is pivotal for maintaining adipocyte homeostasis and preserving insulin responsiveness. The effect of the bioactive fragment of CCK, CCK-8, in regulating adipose AQP7 expression and glycerol efflux was assessed in rats as well as in preadipocytes. Moreover, the involvement of insulin receptors in the effects of CCK-8 was characterized in preadipocytes lacking insulin receptors. CCK-8 induced AQP7 gene expression in rat WAT, concomitantly increasing plasma glycerol concentration. In isolated preadipocytes, CCK-8 also enhanced both AQP7 expression and glycerol leakage. The effects of CCK-8 were independent of the lipolysis rate, as CCK-8 failed to promote fatty acid release by adipocytes. In addition, CCK-8 did not enhance hormone sensitive lipase phosphorylation, which is the rate-limiting step of lipolysis. Moreover, the effects of CCK-8 were dependent on the activation of protein kinase B and PPARγ. Silencing insulin receptor expression inhibited CCK-8-induced Aqp7 expression in preadipocytes. Furthermore, insulin enhanced the effect of CCK-8. CCK regulates AQP7 expression and function, and this effect is dependent on insulin. Accordingly, CCK receptor agonists could be suitable for preserving and improving insulin responsiveness in WAT.

Role of Hydrogen Sulfide and Polysulfides in the Regulation of Lipolysis in the Adipose Tissue: Possible Implications for the Pathogenesis of Metabolic Syndrome.

Hydrogen sulfide (H2S) and inorganic polysulfides are important signaling molecules; however, little is known about their role in the adipose tissue. We examined the effect of H2S and polysulfides on adipose tissue lipolysis. H2S and polysulfide production by mesenteric adipose tissue explants in rats was measured. The effect of Na2S and Na2S4, the H2S and polysulfide donors, respectively, on lipolysis markers, plasma non-esterified fatty acids (NEFA) and glycerol, was examined. Na2S but not Na2S4 increased plasma NEFA and glycerol in a time- and dose-dependent manner. Na2S increased cyclic AMP but not cyclic GMP concentration in the adipose tissue. The effect of Na2S on NEFA and glycerol was abolished by the specific inhibitor of protein kinase A, KT5720. The effect of Na2S on lipolysis was not abolished by propranolol, suggesting no involvement of β-adrenergic receptors. In addition, Na2S had no effect on phosphodiesterase activity in the adipose tissue. Obesity induced by feeding rats a highly palatable diet for 1 month was associated with increased plasma NEFA and glycerol concentrations, as well as greater H2S production in the adipose tissue. In conclusion, H2S stimulates lipolysis and may contribute to the enhanced lipolysis associated with obesity.

Glucose-dependent insulinotropic polypeptide induces lipolysis during stable basal insulin substitution and hyperglycaemia in men with type 1 diabetes: A randomized, double-blind, placebo-controlled, crossover clinical trial.

Glucose-dependent insulinotropic polypeptide (GIP) plays an important role in the glucose and lipid metabolism. We investigated the effects of exogenous GIP on lipid metabolism during time of stable insulin levels. Ten male patients with type 1 diabetes without endogenous insulin secretion (C-peptide-negative, mean[±SD] age 26 ± 4years, body mass index 24[±2]kg/m2 , glycated haemoglobin 56[±8]mmol/mol or 7.3[±0.8]%) were studied in a randomized, double-blind, placebo-controlled, crossover study with continuous intravenous infusions of GIP (4pmol/kg/min) or placebo (saline), during two separate 90-minute hyperglycaemic (12 mmol/L) clamps with basal insulin substitution (0.1-0.2mU/kg/min). Plasma glycerol concentrations increased from baseline during GIP infusion and decreased during placebo infusion (baseline-subtracted area under the curve [bsAUC] 703 ± 407 vs. -262 ± 240 μmol/L × min, respectively; P < 0.001). Free fatty acids (FFAs) increased during GIP infusions (bsAUC 5505 ± 2170 μEq/L × min) and remained unchanged during placebo infusion (bsAUC -74 ± 2363 μEq/L × min), resulting in a significant difference between GIP and placebo infusions (P < 0.001). Plasma concentrations of glucose, insulin, glucagon-like peptide-1 and glucagon were similar during GIP and placebo infusions. GIP increased plasma glycerol and FFAs in patients with type 1 diabetes during hyperglycaemia and stable basal insulin levels. This supports a direct lipolytic effect of GIP at high glucose and low levels of plasma insulin.

648-P: Glucose-Dependent Insulinotropic Polypeptide (GIP) Induces Lipolysis during Stable Basal Insulin Substitution and Hyperglycemia in Men with Type 1 Diabetes

Glucose-dependent insulinotropic polypeptide (GIP) contributes importantly to postprandial insulin secretion, and - perhaps primarily due to this insulinotropic effect - affects glucose and lipid metabolism. We investigated the effects of exogenous GIP on lipid metabolism during hyperglycemia and stable insulin levels. Ten male patients with type 1 diabetes without endogenous insulin secretion (C-peptide negative), aged [mean±SD: 26±4 years; BMI: 24±2 kg/m2; HbA1c 7.3±0.8%) were studied in a randomized, double-blind, crossover study with continuous intravenous infusions of GIP (4 pmol/kg/min) or placebo (saline), during two separate 90-minute hyperglycemic (12 mmol/L) clamps with basal insulin substitution (0.1-0.2 mU/kg/min). Plasma glycerol concentrations increased from baseline during GIP infusions and decreased during placebo infusions (baseline-subtracted area under the curve (bsAUC): 703±407 vs. -262±240 µmol/L × min, respectively, P&amp;lt;0.001). Free fatty acids increased only during GIP infusions (bsAUC: 5,431±6,393 during GIP vs. -74±2,363 µmol/l × min during placebo infusion, P&amp;lt;0.05). Plasma concentrations of glucose, insulin, and glucagon were similar during GIP and placebo infusions (P=NS). Compared to placebo, GIP increased plasma glycerol and free fatty acids in patients with type 1 diabetes during hyperglycemia and stable basal insulin levels. With this experimental design it was possible to clearly identify an important effect of GIP on lipolysis in humans. Disclosure C. N. Nielsen: None. S. M. Nguyen heimbürger: Speaker’s Bureau; Self; AstraZeneca. S. Calanna: Employee; Self; Novo Nordisk A/S. J. J. Holst: Consultant; Self; Novo Nordisk, Other Relationship; Self; Antag Therapeutics, Bainan Biotech, MSD Corporation, Novo Nordisk, Other Relationship; Spouse/Partner; Antag Therapeutics, Bainan Biotech, Synklino ApS. T. Vilsbøll: Consultant; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Gilead Sciences, Inc., Lilly Diabetes, Merck Sharp &amp; Dohme Corp., Mundipharma International, Novo Nordisk, Sanofi, Sun Pharmaceutical Industries Ltd. F. K. Knop: Advisory Panel; Self; MSD Corporation, Novo Nordisk A/S, Sanofi, Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk A/S, Pharmacosmos, Zealand Pharma A/S, Research Support; Self; Novo Nordisk A/S, Zealand Pharma A/S, Speaker’s Bureau; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, MSD Corporation, Novo Nordisk A/S. M. B. Christensen: None.

Effect of Media with Different Glycerol Concentrations on Sheep Red Blood Cells' Viability In Vitro.

Simple SummaryGlycerol is widely used as a feed supplement in ruminant nutrition. However, its administration at moderate and high doses results in an increase in plasma osmolality and in an alteration of red blood cell (RBC) indices. The present study aimed at further elucidating the effect of glycerol on RBCs’ functionality by evaluating the effect of different glycerol concentrations on RBC homeostasis under in vitro conditions. Obtained results showed that glycerol permeates the RBC membrane and leads to hemolysis when glycerol concentration exceeds 200 mg/dL. However, RBCs’ antioxidant defenses appear to protect cell membranes without causing an increase of oxidative stress markers. Moreover, no alteration in RBCs’ intracellular Ca2+ ion concentrations and metabolic activity were found. In conclusion, glycerol-based nutritional treatment should be designed in sheep to avoid exceeding 200 mg/dL glycerol circulating concentration to prevent RBC osmotic stress.The use of high doses of glycerol as a livestock feed supplement is followed by a rapid increase in plasma concentrations and consequently in plasma osmolality. Moreover, glycerol is a highly diffusible molecule that can readily permeate the red blood cell (RBC) membrane following a concentration gradient. A rise in glycerol plasma concentrations can thus alter RBC homeostasis. The present study aimed at investigating both glycerol osmotic effects on sheep RBCs and their oxidative response under in vitro conditions. Sheep blood samples were suspended in media supplemented with increasing glycerol concentrations (0, 25, 50, 100, 150, 200, 250, 300, 350, 400 mg/dL), which reflected those found in vivo in previous studies, and incubated at 37 °C for 4h. Thereafter, osmolality and hemolysis were determined in spent media, while cell extracts were used to assay intracellular concentration of glycerol, ATP, Ca2+ ions, oxidative stress markers and reactive oxygen species (ROS).The study confirmed that glycerol intracellular concentrations are directly related with its concentration in the incubation media, as well as hemolysis (p < 0.001) which increased significantly at glycerol concentrations higher form 200 mg/dL. ROS intracellular level increased at all glycerol concentration tested (p < 0.01) and total thiols decreased at the highest concentrations. However, RBCs proved to be able to cope by activating their antioxidant defense system. Superoxide dismutase activity indeed increased at the highest glycerol concentrations (p < 0.001), while total antioxidant capacity and malonyldialdehyde, a typical product of lipid peroxidation by ROS, did not show significant changes. Moreover, no alterations in intracellular Ca2+ ions and ATP concentrations were found. In conclusion, glycerol-induced hemolysis can be related to the induced osmotic stress. In sheep, nutritional treatments should be designed to avoid reaching glycerol circulating concentrations higher than 200 mg/dL.

Pseudohypertriglyceridemia Can Be Detected By 2D-Diffusion-Ordered 1H-Nuclear Magnetic Resonance Spectroscopy

Background and Aims: Glycerol kinase deficiency (GKD) is an X-linked recessive enzyme defect characterized biochemically by hyperglycerolemia and glyceroluria. In routine laboratories, methods for serum triglycerides determination generally involve hydrolysis of triglycerides to glycerol and free fatty acids, followed by measurement of the glycerol released. Therefore, an elevated plasma glycerol concentration can erroneously result in an overestimation of plasma triglycerides, known as pseudohypertriglyceridemia. The aim of this study was to characterize real lipoprotein profile and triglycerides concentration, in four patients with pseudohypertriglyceridemia, using 1H-Nuclear Magnetic Resonance (1H-NMR) spectroscopy.

GLUTAMINE SUPPLEMENTATION: EFFECTS ON GROWTH HORMONE AND TIME-TRIAL PERFORMANCE AFTER PROLONGED EXERCISE

Dietary glutamine supplementation has been proposed as a potential aid to athletic performance. The purpose of the investigation was to determine if glutamine supplementation might improve cycling performance, perhaps by stimulating growth hormone release, in athletes consuming a high-carbohydrate diet. Six trained young adult men participated in two four-day supplementation trials. In both trials, the subjects underwent an identical carbohydrate-loading regimen of controlled diet (75% carbohydrate) and exercise. The only difference in the trials was whether the subjects ingested dietary supplements of glutamine or glucose placebo. During the first three days of each trial, the diets were supplemented with either glutamine or glucose placebo at a dosage of 150 mg/kg body weight (~10.4 g/d). On the fourth day, the supplements were dissolved in a sports drink (4 g/L). The sports drink initially contained a 6% solution of carbohydrate. On the fourth day the subjects ingested 7 ml/kg of the supplemented sports drink 2 h before exercise, 5 ml/kg 1 h before exercise, and 3 ml/kg after 15, 30, 45, 60, and 90 min of exercise. The total amount of glutamine supplement or placebo consumed on the fourth day was 108 mg/kg or about 7.4 g, of which 3.3 g were consumed before and 4.1 g during exercise. On the fourth day, subjects completed 90 min of cycle ergometry, divided into six 15-min periods, each of which included in sequence 12 min @75% VO2max, 1 min @ 120% VO2max, and 2 min @ 50% VO2max. The 90 min exercise session was immediately followed by 15 min of rest and then a final 20-km time trial at ~85% VO2max. Plasma concentrations of glycerol and free fatty acids and serum growth hormone concentrations were measured before and during exercise, and time-trial performance was recorded. Times (± SEM) to complete the 20-km performance rides were 31.03 ± 0.58 min for the placebo trial and 30.93 ± 0.60 min for the glutamine trial and were not significantly different (P&gt;0.05). There were also no significant effects on serum growth hormone or on plasma glycerol or free fatty acids attributable to glutamine supplementation at any sampling time. In summary, we found no evidence that glutamine supplementation in moderate dosages has any effect on circulating growth hormone, glycerol, or free fatty acids or on time-trial performance in athletes who consume a high-carbohydrate diet

Low temperature-induced variation in plasma biochemical indices and aquaglyceroporin gene expression in the large yellow croaker Larimichthys crocea

Low temperature influences multiple physiological processes in fish. To explore the adaptability of the large yellow croaker (Larimichthys crocea) to low temperature, the concentrations of glycerol, blood urea nitrogen (BUN), and triglycerides (TG) in plasma, as well as the expression levels of metabolism-related genes aqp7 and aqp10, were measured after exposure to low temperature stress and during subsequent rewarming. In addition, tissue samples from the intestine and liver were histologically analyzed. We found that the concentrations of plasma glycerol, BUN, and TG, decreased under low temperature stress, suggesting the metabolism of fat and protein slowed at low temperature. The expression levels of aqp7 and aqp10 mRNA were also downregulated under exposure to low temperature. Interestingly, above plasma indices and gene expression returned to basic levels within 24 h after rewarming. Furthermore, the liver and the intestine were damaged under continuous low temperature stress, whereas they were repaired upon rewarming. From the above results, we concluded that aqp7 and aqp10 genes were sensitive to low temperature, and that the decrease in their expression levels at low temperature might reduce energy consumption by L. crocea. However, the adaptation to low temperature was limited because the key metabolic tissues were damaged under continuous exposure to low temperature. Interestingly, the metabolism of L. crocea was basically back to normal within 24 h of rewarming, showing that it has high capacity of self-recovery.

Inter-individual variation in adaptive capacity at onset of lactation: Linking metabolic phenotype with mitochondrial DNA haplotype in Holstein dairy cows

Modern-day dairy cows express great variation in metabolic capacity to adapt to the onset of lactation. Although breeding programs increased the breeding value for longevity and robustness in the sires, a respective phenotype in female offspring has not been improving as predicted. Fundamental energy generating pathways such as mitochondrial fatty acid oxidation might have a crucial role for robustness and metabolic efficiency in dairy cows. Therefore, mitochondrial enzyme expression was examined in liver samples of one set of animals before and after calving. Furthermore, the mitochondrial DNA sequence was determined for each individual of a second set of animals using liver samples. Results from the first trial indicate that the expression and extent of phosphorylation of acetyl-CoA carboxylase (ACC) is the major key step for modulating fatty acid flux into the mitochondria at early onset of lactation in Holstein dairy cows. In the second trial, mitochondrial DNA sequencing and identification of mutation patterns yielded three major haplotypes. Haplotype H2 was closely associated with liver fat content, plasma glycerol and acyl-carnitine concentrations. The mitochondrial DNA haplotype, which is a feature of the maternal lines, might be related to the inter-individual variation in metabolic capacity of Holstein dairy cows.

Mild Physiologic Hyperglycemia Induces Hepatic Insulin Resistance in Healthy Normal Glucose Tolerant Subjects–Role of Glucagon and Gluconeogenic Substrates

The aim of the present study was to evaluate the effect of a physiologic increase in plasma glucose concentration on endogenous glucose production (EGP) in healthy NGT individuals. 16 NGT subjects [8 with and 8 without family history of T2DM (9M/7F, age = 44± 3 years, BMI = 26 ± 1 kg/m2)] participated in a 3-step hyperinsulinemic (10, 20, 40 mU/m2 min) euglycemic clamp before and after a 48 hour glucose infusion to increase plasma glucose conc by ∼45 mg/dl above baseline (89±4 to 136±4.9 mg/dl). EGP was measured with [3-3H] glucose and gluconeogenic rate was measured following administration of deuterated water. Plasma FFA, glucagon, lactate, glycerol and alanine concentrations also were measured. Following 48 hours of glucose infusion basal EGP increased from 2.05±0.09 to 3.06±0. mg/kg min (p=0.003) and hepatic insulin resistance index (EGP X Fasting Plasma Insulin) increased markedly and similarly (25.1±1.0 vs. 48.3± 3.2, p&amp;lt;0.005). The baseline plasma glucagon concentration tended to be higher following 48 hours of glucose infusion (64±3 vs. 77± 8 pg/ml, p=0.2) while the product of the plasma glucagon and insulin concentrations was markedly increased (540 ± 56 vs. 1336 ± 262, p=0.004). Although the baseline plasma FFA concentration was markedly reduced following 48 hours of glucose infusion (0.482 ±0.to 0.055± 0.01mM), there was no difference in plasma glycerol concentration (13.4±1.2 vs. 13.3 ± 2.2 mg/L p=ns). There were small increases in both the plasma lactate and alanine concentrations. Total body insulin sensitivity declined from 8.75±2.1 to 6.92± 6 mg.kg/min (p&amp;lt;0.05). Conclusion: Chronic (48 hr) physiologic hyperglycemia to levels seen in T2DM increases basal hepatic glucose production and induces hepatic and skeletal muscle insulin resistance in healthy NGT subjects. These results demonstrate, for the first time that glucotoxicity causes resistance to the suppressive effect of insulin on hepatic glucose production. Disclosure D. Tripathy: None. A. Merovci: None. E.R. Maldonado Corchado: None. R. Basu: Research Support; Self; AstraZeneca. R.A. DeFronzo: Speaker-s Bureau; Self; AstraZeneca, Novo Nordisk Inc.. Advisory Panel; Self; AstraZeneca, Novo Nordisk Inc., Janssen Pharmaceuticals, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Elcelyx Therapeutics, Inc., Intarcia Therapeutics, Inc.. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Takeda Pharmaceuticals U.S.A., Inc..

New Zealand blackcurrant extract enhances fat oxidation during prolonged cycling in endurance-trained females

PurposeNew Zealand blackcurrant (NZBC) extract has previously been shown to increase fat oxidation during prolonged exercise, but this observation is limited to males. We examined whether NZBC intake also increases fat oxidation during prolonged exercise in females, and whether this was related to greater concentrations of circulating fatty acids.MethodsIn a randomised, crossover, double-blind design, 16 endurance-trained females (age: 28 ± 8 years, BMI: 21.3 ± 2.1 kg·m−2, VO2max: 43.7 ± 1.1 ml·kg−1·min−1) ingested 600 mg·day−1 NZBC extract (CurraNZ™) or placebo (600 mg·day−1 microcrystalline cellulose) for 7 days. On day 7, participants performed 120 min cycling at 65% VO2max, using online expired air sampling with blood samples collected at baseline and at 15 min intervals throughout exercise for analysis of glucose, NEFA and glycerol.ResultsNZBC extract increased mean fat oxidation by 27% during 120 min moderate-intensity cycling compared to placebo (P = 0.042), and mean carbohydrate oxidation tended to be lower (P = 0.063). Pre-exercise, plasma NEFA (P = 0.034) and glycerol (P = 0.051) concentrations were greater following NZBC intake, although there was no difference between conditions in the exercise-induced increase in plasma NEFA and glycerol concentrations (P > 0.05). Mean fat oxidation during exercise was moderately associated with pre-exercise plasma NEFA concentrations (r = 0.45, P = 0.016).ConclusionsIntake of NZBC extract for 7 days elevated resting concentrations of plasma NEFA and glycerol, indicative of higher lipolytic rates, and this may underpin the observed increase in fat oxidation during prolonged cycling in endurance-trained females.

Effect of Sacubitril/Valsartan on Exercise-Induced Lipid Metabolism in Patients With Obesity and Hypertension.

URL: https://www.clinicaltrials.gov. Unique identifier: NCT01631864.

NMR-based metabolomic study on the toxicological effects of pesticide, diazinon on adaptation to sea water by endangered Persian sturgeon, Acipenser persicus fingerlings

NMR-based metabolomics was applied to explore metabolic impacts of diazinon on sea water adaptation of Persian sturgeon fingerlings, Acipenser persicus. Fingerlings were exposed to sub-lethal concentrations of diazinon in freshwater (FW) for 96 h (short-term trial) and 12 days (long-term trial) and then exposed in brackish water (BW) (12 mg L−1 salinity) for 24 h. After 96 h and 12 days exposure in FW, identified metabolites (amino acids, osmolytes, energy metabolites) showed different change-patterns compared to control group (P < 0.05) as follow: (A) short-term trial: higher plasma levels of glucose, lactate (in all diazinon-exposed fish), acetate and acetoacetate (in 0.9 mg L−1diazinon treatment); lower levels of creatine (in all diazinon-exposed fish), trimethylamine-N-oxide, choline, taurine, betaine, N,N-dimethylglycine and almost all amino acids in fish exposed to high concentrations of diazinon (0.54 and 0.9 mg L−1 diazinon). (B) Long-term trial: higher plasma levels of lipid oxidation metabolites and almost all amino acids in fish exposed to 0.54 and 0.9 mg L−1 diazinon; lower levels of creatine, trimethylamine-N-oxide, N,N-dimethylglycine, betaine, choline (in all diazinon-exposed fish), glucose (in 0.54 and 0.9 mg L−1diazinon treatments) and taurine (in 0.9 mg L−1 diazinon treatment).When fish were exposed in BW for 24 h, the plasma levels of osmolytes decreased significantly in almost all experimental groups of short-term and long-term trial (P < 0.05). In short-term trial, the plasma levels of glucose in all groups and lactate in 0.18 and 0.54 mg L−1 diazinon treatments increased after salinity challenge (P < 0.05). However, a significant decrease was observed in lactate levels in 0.9 mg L−1 diazinon treatment (P < 0.05). Also, the plasma levels of amino acids decreased mostly in fish of control group than exposed fish (P < 0.05). The plasma glycerol concentration showed a significant decrease only in fish of 0.54 mg L−1 diazinon treatment (P < 0.05). In long term trial, the energetic metabolites (acetate, acetoacetate, glycerol) showed significant increases mostly in fish exposed to high concentrations of diazinon (P < 0.05). Phosphocreatine was detected only in groups exposed to 0.54 and 0.9 mg L−1 diazinon. Some amino acids decreased in control and diazinon-exposed groups while glycine (in control and 0.18 mg L−1 diazinon treatment), glutamine and alanine (in 0.9 mg L−1 diazinon treatment) elevated significantly after 24 h acclimation in BW (P < 0.05). Our results may help to understand the effects of pesticides on fish osmoregulation from a metabolic approach.

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.