Metabolic Effects of Acute Hyperketonaemia in Man before and during An Hyperinsulinaemic Euglycaemic Clamp

1994 ◽  
Vol 86 (6) ◽  
pp. 677-687 ◽  
Author(s):  
J. Webber ◽  
E. Simpson ◽  
H. Parkin ◽  
I. A. MacDonald
Keyword(s):  
Adipose Tissue ◽  
Glucose Uptake ◽  
Glucose Oxidation ◽  
Respiratory Exchange Ratio ◽  
Saline Infusion ◽  
Metabolic Effects ◽  
Whole Body ◽  
Glucose Storage ◽  
Adipose Tissue Lipolysis ◽  
Subcutaneous Abdominal Adipose Tissue

1. The effects of acutely raising blood ketone body levels to those seen after 72 h of starvation were examined in 10 subjects after an overnight fast. Metabolic rate and respiratory exchange ratio were measured with indirect calorimetry before and during an insulin—glucose clamp. Arteriovenous differences were measured across forearm and subcutaneous abdominal adipose tissue. 2. In response to the clamp the respiratory exchange ratio rose from 0.82 to 0.83 during 3-hydroxybutyrate infusion and from 0.83 to 0.94 during control (saline) infusion (P < 0.001). 3. Forearm glucose uptake at the end of the clamp was 4.02 ± 0.95 (3-hydroxybutyrate infusion) and 7.09 ± 1.24 mmol min−1 100 ml−1 forearm (saline infusion). Whole body glucose uptake at the end of the clamp was 72.8 ± 7.9 (3-hydroxybutyrate infusion) and 51.0 ± 3.0 (saline infusion) mmol min−1 kg−1 body weight−1. 4. 3-Hydroxybutyrate infusion reduced the baseline abdominal venous—arterialized venous glycerol difference from 84 ± 28 to 25 ± 12 mmol/l and the non-esterified fatty acid difference from 0.60 ± 0.17 to 0.02 ± 0.09 mmol/l (P < 0.05 versus saline infusion). 5. Hyperketonaemia reduces adipose tissue lipolysis and decreases insulin-mediated forearm glucose uptake. Hyperketonaemia appears to prevent insulin-stimulated glucose oxidation, but does not reduce insulin-mediated glucose storage.

Endurance training and GH administration in elderly women: effects on abdominal adipose tissue lipolysis

2001 ◽  
Vol 280 (6) ◽  
pp. E886-E897 ◽  
Author(s):  
Kai Henrik Wiborg Lange ◽  
Jeanne Lorentsen ◽  
Fredrik Isaksson ◽  
Anders Juul ◽  
Michael Højby Rasmussen ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Training Program ◽  
Endurance Training ◽  
Elderly Women ◽  
Fat Oxidation ◽  
Whole Body ◽  
Abdominal Adipose Tissue ◽  
Before And After ◽  
Adipose Tissue Lipolysis ◽  
Subcutaneous Abdominal Adipose Tissue

In the present study, the effect of endurance training alone and endurance training combined with recombinant human growth hormone (rhGH) administration on subcutaneous abdominal adipose tissue lipolysis was investigated. Sixteen healthy women [age 75 ± 2 yr (mean ± SE)] underwent a 12-wk endurance training program on a cycle ergometer. rhGH was administered in a randomized, double-blinded, placebo-controlled design in addition to the training program. Subcutaneous abdominal adipose tissue lipolysis was estimated by means of microdialysis combined with measurements of subcutaneous abdominal adipose tissue blood flow (ATBF; 133Xe washout). Whole body fat oxidation was estimated simultaneously by indirect calorimetry. Before and after completion of the training program, measurements were performed both at rest and during 60 min of continuous cycling at a workload corresponding to 60% of pretraining peak oxygen uptake. Endurance training alone did not affect subcutaneous abdominal adipose tissue lipolysis either at rest or during exercise, as reflected by identical levels of interstitial adipose tissue glycerol, subcutaneous abdominal ATBF, and plasma nonesterified fatty acids before and after completion of the training program. Similarly, no effect on subcutaneous abdominal adipose tissue lipolysis was observed when combining endurance training with rhGH administration. However, in both the placebo and the GH groups, fat oxidation was significantly increased during exercise performed at the same absolute workload after completion of the training program. We conclude that the changed lipid metabolism during exercise observed after endurance training alone or after endurance training combined with rhGH administration is not due to alterations in subcutaneous abdominal adipose tissue metabolism in elderly women.

Subcutaneous Abdominal Adipose Tissue Lipolysis During Exercise Determined by Arteriovenous Measurements in Older Women

2002 ◽  
Vol 50 (2) ◽  
pp. 275-281 ◽  
Author(s):  
Kai Henrik Wiborg Lange ◽  
Jeanne Lorentsen ◽  
Fredrik Isaksson ◽  
Lene Simonsen ◽  
Anders Juul ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Older Women ◽  
Abdominal Adipose Tissue ◽  
Adipose Tissue Lipolysis ◽  
Subcutaneous Abdominal Adipose Tissue

Thermogenic response to epinephrine in the forearm and abdominal subcutaneous adipose tissue

1992 ◽  
Vol 263 (5) ◽  
pp. E850-E855 ◽  
Author(s):  
L. Simonsen ◽  
J. Bulow ◽  
J. Madsen ◽  
N. J. Christensen
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Energy Expenditure ◽  
Oxygen Uptake ◽  
Glucose Uptake ◽  
Subcutaneous Adipose Tissue ◽  
Whole Body ◽  
Epinephrine Infusion ◽  
Basal Period ◽  
Subcutaneous Adipose

Whole body energy expenditure, thermogenic and metabolic changes in the forearm, and intercellular glucose concentrations in subcutaneous adipose tissue on the abdomen determined by microdialysis were measured during epinephrine infusion in healthy subjects. After a control period, epinephrine was infused at rates of 0.2 and 0.4 nmol.kg-1 x min-1. Whole body resting energy expenditure was 4.36 +/- 0.56 (SD) kJ/min. Energy expenditure increased to 5.14 +/- 0.74 and 5.46 +/- 0.79 kJ/min, respectively (P < 0.001), during the epinephrine infusions. Respiratory exchange ratio was 0.80 +/- 0.04 in the resting state and did not change. Local forearm oxygen uptake was 3.9 +/- 1.3 mumol.100 g-1 x min-1 in the basal period. During epinephrine infusion, it increased to 5.8 +/- 2.1 (P < 0.03) and 7.5 +/- 2.3 mumol.100 g-1 x min-1 (P < 0.001). Local forearm glucose uptake was 0.160 +/- 0.105 mumol.100 g-1 x min-1 and increased to 0.586 +/- 0.445 and 0.760 +/- 0.534 mumol.100 g-1 x min-1 (P < 0.025). The intercellular glucose concentration in the subcutaneous adipose tissue on the abdomen was equal to the arterial concentration in the basal period but did not increase as much during infusion of epinephrine, indicating glucose uptake in adipose tissue in this condition. If it is assumed that forearm skeletal muscle is representative for the average skeletal muscle, it can be calculated that on average 40% of the enhanced whole body oxygen uptake induced by infusion of epinephrine is taking place in skeletal muscle. It is proposed that adipose tissue may contribute to epinephrine-induced thermogenesis.

Fat Metabolism in Heavy Exercise

1980 ◽  
Vol 59 (6) ◽  
pp. 469-478 ◽  
Author(s):  
N. L. Jones ◽  
G. J. F. Heigenhauser ◽  
A. Kuksis ◽  
C. G. Matsos ◽  
J. R. Sutton ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Free Fatty Acids ◽  
Respiratory Exchange Ratio ◽  
Fat Metabolism ◽  
Maximum Power ◽  
Oxygen Intake ◽  
Heavy Exercise ◽  
Heavy Work ◽  
Adipose Tissue Lipolysis

1. To investigate differences between the metabolic effects of light and heavy exercise, five healthy males (mean maximal oxygen intake 3.92 litres/min) exercised for 40 min at 36% maximum power (light work) and 70% maximum power (heavy work) on separate days, after an overnight fast. 2. A steady state was achieved in both studies between 20 and 40 min in: oxygen intake (1.42 and 2.64 litres/min respectively); respiratory exchange ratio (0.89 and 1.01); plasma lactate concentration (1.78 and 9.94 mmol/l). 3. Plasma palmitate turnover rate (14C) was unchanged from resting values in light work but was decreased by 40% (from 104 ± 16 to 63 ± 8 μmol/min) in heavy work. Heavy work was associated with falls in the plasma concentrations of all free fatty acids measured: palmitic acid (C16:0), oleic acid (C18:1), stearic acid (C18:0), linoleic acid (C18:2) and palmitoleic acid (C16:1). 4. In contrast to the fall in palmitate turnover the increase in plasma glycerol was greater in heavy exercise (0.054–0.229 mmol/l) than in light exercise (0.053–0.094 mmol/l), suggesting that lipolysis was occurring which did not lead to influx of free fatty acids into plasma. 5. In light exercise fat metabolism may be controlled to favour adipose tissue lipolysis and extraction of free fatty acids by muscle from the circulation, whereas in heavy exercise adipose tissue lipolysis is inhibited and hydrolysis of muscle triglycerides may play a more important part. 6. The finding of a high respiratory exchange ratio may not exclude the use of fat as a major fuel source in exercise associated with lactate production.

45 Unravelling the Unique Burn-induced Temporal Alterations in Adipose Tissue Metabolism

2020 ◽  
Vol 41 (Supplement_1) ◽  
pp. S30-S30
Author(s):  
Carly M Knuth ◽  
Chris Auger ◽  
Abdikarim Abdullahi ◽  
Marc G Jeschke
Keyword(s):  
Adipose Tissue ◽  
Murine Model ◽  
Burn Injury ◽  
Total Body Surface Area ◽  
Time Dependent ◽  
Metabolic Effects ◽  
Whole Body ◽  
Potential Contribution ◽  
Significant Difference ◽  
Tissue Browning

Abstract Introduction A severe burn elicits a systemic hypermetabolic response that substantially alters the function of multiple organs and contributes to increased morbidity and mortality. A consequence of hypermetabolism is the activation of UCP1-mediated browning of white adipose tissue (WAT), which may further facilitate the hypermetabolic response. In this study, we aimed to provide comprehensive characterization of the acute and long term pathophysiological responses to burns to determine the persistence of adipose tissue browning and its potential contribution to the hypermetabolic response. Methods Mice were subjected to either a 30% total body surface area (TBSA) scald burn or were denoted sham. Body weight and food intake were monitored throughout the duration of the study. Cohorts were sacrificed at 6hrs, 1, 3, 5, 7, 14, 30 and 60d post-burn and adipose tissue depots were harvested. Mitochondrial respiration, protein expression, and morphology in adipose tissues were assessed. Results Despite consuming considerably more food, the burn group lost significantly more weight throughout the duration of the study. We also detected increases in free fatty acids and interleukin-6, markers of whole-body lipolysis and inflammation, respectively. At the tissue level, eWAT mass significantly decreased over time, suggesting that this depot provides substrate to fuel the hypermetabolic response. This was further supported by a decrease in adipocyte area and an increase in lipolytic markers which remains significant up until 60d post-burn relative to sham. There were no significant difference in iWAT mass, however we detected significant increases in the protein content of UCP1, the master regulator of adipose tissue browning, as early as day 3 which persisted until day 60. This was corroborated by the presence of UCP1+ adipocytes. Conclusions Consistent with previous human studies, a burn injury elicits a dynamic response that cannot be simply characterized by a single timepoint. The alterations that occur in adipose tissue are depot-specific, time-dependent, and this notion likely extends to other metabolic tissues. Further, we demonstrate that in our 30% TBSA burn murine model, the effects of the hypermetabolic response persist for up to 60 days following initial injury. Applicability of Research to Practice Our data indicate the hypermetabolic response persists for up to 60 days, the equivalent of approximately 7 years in humans. This underscores the severity of adipose tissue browning and potentially provides an explanation as to how the hypermetabolic response persists even after the wound has healed. Moreover, providing a comprehensive map of the time-dependent changes in a murine model gives clinicians a better indication of the metabolic effects in a burn patient and will contribute to the development of effective, targeted treatments.

scholarly journals Metabolic effects of low cortisol during exercise in humans

1998 ◽  
Vol 84 (3) ◽  
pp. 939-947 ◽  
Author(s):  
Pedro Del Corral ◽  
Edward T. Howley ◽  
Mike Hartsell ◽  
Muhammad Ashraf ◽  
Mary Sue Younger
Keyword(s):  
Amino Acids ◽  
Growth Hormone ◽  
Plasma Glucose ◽  
Respiratory Exchange Ratio ◽  
Branched Chain Amino Acids ◽  
Physiological Effect ◽  
Metabolic Effects ◽  
Whole Body ◽  
Branched Chain ◽  
Exercise In Humans

This study examined the physiological effect of reduced plasma cortisol (C) during prolonged exercise in humans. The effects of normal C (NC) were compared with metyrapone-induced low C (LC) on plasma substrate availability and the respiratory exchange ratio during 2 h of exercise at ∼60% peak O2 consumption in nine subjects. The C responses were compared with preexercise (Pre) levels and with a rest day (Con). At rest, C was attenuated by ∼70% for LC compared with NC. At rest, plasma glucose, lactate, glycerol, β-hydroxybutyrate, alanine, branched-chain amino acids, insulin, glucagon, growth hormone, epinephrine, and norepinephrine were similar under LC and NC ( P > 0.05). During exercise under NC, plasma C increased compared with Pre, whereas it remained unchanged during LC. During NC, plasma C was elevated at 90 min (compared with Con) and at 120 min (compared with Con and Pre). During exercise, plasma glucose decreased to the same extent and lactate was similar under both conditions, whereas plasma glycerol, β-hydroxybutyrate, alanine, and branched-chain amino acids were higher ( P < 0.01) under NC. Plasma insulin declined ( P = 0.01) to a greater extent under LC, whereas growth hormone, epinephrine, and norepinephrine tended to be higher (0.05 ≤ P ≤ 0.10). Plasma glucagon increased under both conditions ( P < 0.01). The respiratory exchange ratio did not differ between conditions. We conclude that, during exercise, 1) C accelerates lipolysis, ketogenesis, and proteolysis; 2) under LC, glucoregulatory hormone adjustments maintain glucose homeostasis; and 3) LC does not alter whole body substrate utilization or the ability to complete 2 h of moderate exercise.

scholarly journals Thyroid Hormone Effects on Glucose Disposal in Patients With Insulin Receptor Mutations

2019 ◽  
Vol 105 (3) ◽  
pp. e158-e171 ◽  
Author(s):  
Yevgeniya S Kushchayeva ◽  
Megan Startzell ◽  
Elaine Cochran ◽  
Sungyoung Auh ◽  
Hilal Sekizkardes ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Thyroid Hormone ◽  
Insulin Receptor ◽  
Glucose Uptake ◽  
Receptor Gene ◽  
Whole Body ◽  
Glucose Disposal ◽  
Isotopic Tracers ◽  
Insulin Receptor Gene ◽  
Brown Adipose

Abstract Context Patients with mutations of the insulin receptor gene (INSR) have extreme insulin resistance and are at risk for early morbidity and mortality from diabetes complications. A case report suggested that thyroid hormone could improve glycemia in INSR mutation in part by increasing brown adipose tissue (BAT) activity and volume. Objective To determine if thyroid hormone increases tissue glucose uptake and improves hyperglycemia in INSR mutation. Design Single-arm, open-label study of liothyronine. Setting National Institutes of Health. Participants Patients with homozygous (n = 5) or heterozygous (n = 2) INSR mutation. Intervention Liothyronine every 8 hours for 2 weeks (n = 7); additional 6 months’ treatment in those with hemoglobin A1c (HbA1c) &gt; 7% (n = 4). Outcomes Whole-body glucose uptake by isotopic tracers; tissue glucose uptake in muscle, white adipose tissue (WAT) and BAT by dynamic [18F] fluorodeoxyglucose positron emission tomography/computed tomography; HbA1c. Results There was no change in whole-body, muscle, or WAT glucose uptake from baseline to 2 weeks of liothyronine. After 6 months, there was no change in HbA1c (8.3 ± 1.2 vs 9.1 ± 3.0%, P = 0.27), but there was increased whole-body glucose disposal (22.8 ± 4.9 vs 30.1 ± 10.0 µmol/kg lean body mass/min, P = 0.02), and muscle (0.7 ± 0.1 vs 2.0 ± 0.2 µmol/min/100 mL, P &lt; 0.0001) and WAT glucose uptake (1.2 ± 0.2 vs 2.2 ± 0.3 µmol/min/100 mL, P &lt; 0.0001). BAT glucose uptake could not be quantified because of small volume. There were no signs or symptoms of hyperthyroidism. Conclusion Liothyronine administered at well-tolerated doses did not improve HbA1c. However, the observed increases in muscle and WAT glucose uptake support the proposed mechanism that liothyronine increases tissue glucose uptake. More selective agents may be effective at increasing tissue glucose uptake without thyroid hormone–related systemic toxicity. Clinical Trial Registration Number: NCT02457897; https://clinicaltrials.gov/ct2/show/NCT02457897.

Overexpression of Foxf2 in adipose tissue is associated with lower levels of IRS1 and decreased glucose uptake in vivo

2010 ◽  
Vol 298 (3) ◽  
pp. E548-E554 ◽  
Author(s):  
Rickard Westergren ◽  
Daniel Nilsson ◽  
Mikael Heglind ◽  
Zahra Arani ◽  
Mats Grände ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Tolerance ◽  
Glucose Uptake ◽  
Target Genes ◽  
Whole Body ◽  
Wild Type ◽  
Intravenous Glucose ◽  
Downstream Target ◽  
Protein Levels

Many members of the forkhead genes family of transcription factors have been implicated as important regulators of metabolism, in particular, glucose homeostasis, e.g., Foxo1, Foxa3, and Foxc2. The purpose of this study was to exploit the possibility that yet unknown members of this gene family play a role in regulating glucose tolerance in adipocytes. We identified Foxf2 in a screen for adipose-expressed forkhead genes. In vivo overexpression of Foxf2 in an adipose tissue-restricted fashion demonstrated that such mice display a significantly induced insulin secretion in response to an intravenous glucose load compared with wild-type littermates. In response to increased Foxf2 expression, insulin receptor substrate 1 (IRS1) mRNA and protein levels are significantly downregulated in adipocytes; however, the ratio of serine vs. tyrosine phosphorylation of IRS1 seems to remain unaffected. Furthermore, adipocytes overexpressing Foxf2 have a significantly lower insulin-mediated glucose uptake compared with wild-type adipocytes. These findings argue that Foxf2 is a previously unrecognized regulator of cellular and systemic whole body glucose tolerance, at least in part, due to lower levels of IRS1. Foxf2 and its downstream target genes can provide new insights with regard to identification of novel therapeutic targets.

scholarly journals ATGL-dependent white adipose tissue lipolysis controls hepatocyte PPARα activity

2021 ◽  
Author(s):  
Anne Fougerat ◽  
Gabriele Schoiswohl ◽  
Arnaud Polizzi ◽  
Marion Régnier ◽  
Carina Wagner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Expression Analysis ◽  
Cold Exposure ◽  
Adrenergic Receptor ◽  
Whole Body ◽  
Fibroblast Growth Factor 21 ◽  
Genome Expression ◽  
Adipose Tissue Lipolysis

ABSTRACTObjectiveIn hepatocytes, peroxisome proliferator-activated receptor α (PPARα) acts as a lipid sensor that regulates hepatic lipid catabolism during fasting and orchestrates a genomic response required for whole-body homeostasis. This includes the biosynthesis of ketone bodies and the secretion of the starvation hormone fibroblast growth factor 21 (FGF21). Several lines of evidence suggest that adipose tissue lipolysis contributes to this specific process. However, whether adipose tissue lipolysis is a dominant signal for the extensive remodeling of liver gene expression dependent on PPARα has not been investigated.MethodsFirst, using mice lacking adipose tissue lipolysis through adipocyte-specific deletion of adipose triglyceride lipase (ATGL), we characterized the responses dependent on adipocyte ATGL during fasting. Next, we performed liver whole genome expression analysis in fasted mice upon deletion of adipocyte ATGL or hepatocyte PPARα. Finally, we tested the consequences of hepatocyte-specific PPARα deficiency during pharmacological induction of adipocyte lipolysis with a β3-adrenergic receptor agonist.ResultsIn the absence of ATGL in adipocytes, ketone body and FGF21 productions were impaired in response to starvation. Liver transcriptome analysis revealed that adipocyte ATGL is critical for regulation of hepatic gene expression during fasting and highlighted a strong enrichment in PPARα target genes in this condition. Genome expression analysis confirmed that a large set of fasting-induced genes are sensitive to both ATGL and PPARα. Adipose tissue lipolysis induced by acute activation of the β3-adrenergic receptor also triggered PPARα-dependent responses in the liver, supporting a role for adipocyte-derived fatty acids as dominant signals for hepatocyte PPARα activity. In addition, the absence of hepatocyte PPARα altered brown adipose tissue (BAT) morphology and reduced UCP1 expression upon stimulation of the β3-adrenergic receptor. In agreement with this finding, mice lacking hepatocyte PPARα showed decreased tolerance to acute cold exposure.ConclusionsThese results underscore the central role of hepatocyte PPARα in the sensing of adipocyte-derived fatty acids and reveal that its activity is essential for full activation of BAT. Intact PPARα activity in hepatocytes is required for cross-talk between adipose tissues and the liver during fat mobilization during fasting and cold exposure.

Specific adaptations in muscle and adipose tissue in response to chronic systemic glucose oversupply in rats

1997 ◽  
Vol 273 (1) ◽  
pp. E1-E9 ◽  
Author(s):  
D. R. Laybutt ◽  
D. J. Chisholm ◽  
E. W. Kraegen
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Glucose Infusion ◽  
Whole Body ◽  
Glucose Disposal ◽  
Saline Control ◽  
Slow Increase ◽  
Glucose Clearance

Rats minimize hyperglycemia during chronic glucose infusion, but the metabolic processes are unclear. We investigated the tissues involved and the role of altered insulin sensitivity. Cannulated rats were infused with glucose (40 mg.kg-1.min-1) for 1 or 4 days or with saline (control). Hyperglycemia at 1 day (15.3 +/- 1.0 mM) was absent at 4 days (7.5 +/- 0.3 mM), but hyperinsulinemia persisted. Whole body glucose disposal was similarly elevated at 1 and 4 days, implying increased glucose clearance at 4 days (2-fold, P < 0.001). Muscle glucose uptake and glycogen content declined in glucose-infused rats from 1 to 4 days, whereas white adipose tissue (WAT) glucose uptake (6-fold, P < 0.001) and lipogenesis (3-fold, P < 0.001) increased. Muscle and liver triglyceride were doubled at both 1 and 4 days (P < 0.05 vs. control). Insulin sensitivity (assessed during euglycemic clamps) decreased in muscle to 34% of control at 1 and 4 days (P < 0.001 vs. control) and increased fivefold in WAT from 1 to 4 days (P < 0.05). Thus chronic glucose infusion results in a slow increase in efficiency of glucose clearance with enhanced WAT glucose uptake, lipogenesis, and insulin action. In contrast, the adaptation reduces glucose oversupply to muscle. Muscle shows sustained insulin resistance, with lipid accumulation a possible contributing factor.

Sign in / Sign up

Export Citation Format

Share Document