Sprint interval exercise training reduces intrahepatic, visceral and subcutaneous abdominal fat despite no change in body weight, but has variable effects on whole-body insulin sensitivity

Exercise training is a powerful strategy to prevent and combat cardiovascular and metabolic diseases, although the integrative nature of the training-induced adaptations is not completely understood. We show that chronic blockade of histamine H1/H2 receptors led to marked impairments of microvascular and mitochondrial adaptations to interval training in humans. Consequently, functional adaptations in exercise capacity, whole-body glycemic control, and vascular function were blunted. Furthermore, the sustained elevation of muscle perfusion after acute interval exercise was severely reduced when H1/H2 receptors were pharmaceutically blocked. Our work suggests that histamine H1/H2 receptors are important transducers of the integrative exercise training response in humans, potentially related to regulation of optimal post-exercise muscle perfusion. These findings add to our understanding of how skeletal muscle and the cardiovascular system adapt to exercise training, knowledge that will help us further unravel and develop the exercise-is-medicine concept.

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Effect of training on insulin binding to rat skeletal muscle sarcolemmal vesicles

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1986.250.5.e570 ◽

1986 ◽

Vol 250 (5) ◽

pp. E570-E575

Author(s):

G. K. Grimditch ◽

R. J. Barnard ◽

S. A. Kaplan ◽

E. Sternlicht

Keyword(s):

Skeletal Muscle ◽

Insulin Sensitivity ◽

Exercise Training ◽

Insulin Binding ◽

Whole Body ◽

Rat Skeletal Muscle ◽

Binding Studies ◽

Muscle Enzyme ◽

Intravenous Glucose ◽

High Affinity

We examined the hypothesis that the exercise training-induced increase in skeletal muscle insulin sensitivity is mediated by adaptations in insulin binding to sarcolemmal (SL) insulin receptors. Insulin binding studies were performed on rat skeletal muscle SL isolated from control and trained rats. No significant differences were noted between groups in body weight or fat. An intravenous glucose tolerance test showed an increase in whole-body insulin sensitivity with training, and specific D-glucose transport studies on isolated SL vesicles indicated that this was due in part to adaptations in skeletal muscle. Enzyme marker analyses revealed no differences in yield, purity, or contamination of SL membranes between the two groups. Scatchard analyses indicated no significant differences in the number of insulin binding sites per milligram SL protein on the high-affinity (15.0 +/- 4.1 vs. 18.1 +/- 6.4 X 10(9)) or on the low-affinity portions (925 +/- 80 vs. 884 +/- 106 X 10(9)) of the curves. The association constants of the high-affinity (0.764 +/- 0.154 vs. 0.685 +/- 0.264 X 10(9) M-1) and of the low affinity sites (0.0096 +/- 0.0012 vs. 0.0102 +/- 0.0012 X 10(9) M-1) also were similar. These results do not support the hypothesis that the increased sensitivity to insulin after exercise training is due to changes in SL insulin receptor binding.

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Lipid Metabolism Links Nutrient-Exercise Timing to Insulin Sensitivity in Men Classified as Overweight or Obese

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgz104 ◽

2019 ◽

Vol 105 (3) ◽

pp. 660-676 ◽

Cited By ~ 2

Author(s):

Robert M Edinburgh ◽

Helen E Bradley ◽

Nurul-Fadhilah Abdullah ◽

Scott L Robinson ◽

Oliver J Chrzanowski-Smith ◽

...

Keyword(s):

Insulin Sensitivity ◽

Exercise Training ◽

Whole Body ◽

Moderate Intensity ◽

Type I ◽

Training Study ◽

Exercise Timing ◽

Lipid Utilization ◽

Acute Study ◽

Intramuscular Lipid

Abstract Context Pre-exercise nutrient availability alters acute metabolic responses to exercise, which could modulate training responsiveness. Objective To assess acute and chronic effects of exercise performed before versus after nutrient ingestion on whole-body and intramuscular lipid utilization and postprandial glucose metabolism. Design (1) Acute, randomized, crossover design (Acute Study); (2) 6-week, randomized, controlled design (Training Study). Setting General community. Participants Men with overweight/obesity (mean ± standard deviation, body mass index: 30.2 ± 3.5 kg⋅m-2 for Acute Study, 30.9 ± 4.5 kg⋅m-2 for Training Study). Interventions Moderate-intensity cycling performed before versus after mixed-macronutrient breakfast (Acute Study) or carbohydrate (Training Study) ingestion. Results Acute Study—exercise before versus after breakfast consumption increased net intramuscular lipid utilization in type I (net change: –3.44 ± 2.63% versus 1.44 ± 4.18% area lipid staining, P < 0.01) and type II fibers (–1.89 ± 2.48% versus 1.83 ± 1.92% area lipid staining, P < 0.05). Training Study—postprandial glycemia was not differentially affected by 6 weeks of exercise training performed before versus after carbohydrate intake (P > 0.05). However, postprandial insulinemia was reduced with exercise training performed before but not after carbohydrate ingestion (P = 0.03). This resulted in increased oral glucose insulin sensitivity (25 ± 38 vs –21 ± 32 mL⋅min-1⋅m-2; P = 0.01), associated with increased lipid utilization during exercise (r = 0.50, P = 0.02). Regular exercise before nutrient provision also augmented remodeling of skeletal muscle phospholipids and protein content of the glucose transport protein GLUT4 (P < 0.05). Conclusions Experiments investigating exercise training and metabolic health should consider nutrient-exercise timing, and exercise performed before versus after nutrient intake (ie, in the fasted state) may exert beneficial effects on lipid utilization and reduce postprandial insulinemia.

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Low-Calorie Diet Plus Interval Exercise Training Improves Metabolic Flexibility and Insulin Sensitivity in Obese Women

Medicine & Science in Sports & Exercise ◽

10.1249/01.mss.0000535819.70552.27 ◽

2018 ◽

Vol 50 (5S) ◽

pp. 222

Author(s):

Nicole M. Gilbertson ◽

Natalie Z.M. Eichner ◽

Emily M. Heiston ◽

Monique Francois ◽

Julian M. Gaítan ◽

...

Keyword(s):

Insulin Sensitivity ◽

Exercise Training ◽

Metabolic Flexibility ◽

Obese Women ◽

Low Calorie ◽

Interval Exercise ◽

Low Calorie Diet ◽

Calorie Diet

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Effect of metformin on substrate utilization after exercise training in adults with impaired glucose tolerance

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2012-0433 ◽

2013 ◽

Vol 38 (4) ◽

pp. 427-430 ◽

Cited By ~ 12

Author(s):

Steven K. Malin ◽

Barry Braun

Keyword(s):

Blood Glucose ◽

Insulin Sensitivity ◽

Exercise Training ◽

Glucose Tolerance ◽

Oxygen Uptake ◽

Indirect Calorimetry ◽

Substrate Utilization ◽

Peak Oxygen Uptake ◽

Whole Body ◽

Glucose Kinetics

Metformin attenuates the higher insulin sensitivity that occurs with exercise training. Sixteen people with prediabetes trained for 10 weeks while taking metformin (n = 8) or placebo (n = 8). Substrate utilization was assessed using glucose kinetics and indirect calorimetry. After training, exercise whole-body fat oxidation was higher and glycogen use lower (p < 0.05), with no differences between groups. Blood glucose use was unchanged. Training-induced enhancement of insulin sensitivity (clamp) correlated with higher peak oxygen uptake (r = 0.70; p < 0.05), but was independent of glucose kinetic and substrate metabolism.

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Acquired obesity is associated with increased liver fat, intra-abdominal fat, and insulin resistance in young adult monozygotic twins

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00381.2004 ◽

2005 ◽

Vol 288 (4) ◽

pp. E768-E774 ◽

Cited By ~ 63

Author(s):

Kirsi Hannele Pietiläinen ◽

Aila Rissanen ◽

Jaakko Kaprio ◽

Sari Mäkimattila ◽

Anna-Maija Häkkinen ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Monozygotic Twins ◽

Fat Distribution ◽

Population Based ◽

Abdominal Fat ◽

Liver Fat ◽

Whole Body ◽

Fasting Insulin ◽

Impaired Insulin

We determined whether acquired obesity is associated with increases in liver or intra-abdominal fat or impaired insulin sensitivity by studying monozygotic (MZ) twin pairs discordant and concordant for obesity. We studied nineteen 24- to 27-yr-old MZ twin pairs, with intrapair differences in body weight ranging from 0.1 to 24.7 kg [body mass index (BMI) range 20.0–33.9 kg/m2], identified from a population-based FinnTwin16 sample. Fat distribution was determined by magnetic resonance imaging, percent body fat by dual-energy X-ray absorptiometry, liver fat by proton spectroscopy, insulin sensitivity by measuring the fasting insulin concentration, and whole body insulin sensitivity by the euglycemic insulin clamp technique. Intrapair differences in BMI were significantly correlated with those in intra-abdominal fat ( r = 0.82, P < 0.001) and liver fat ( r = 0.57, P = 0.010). Intrapair differences in fasting insulin correlated with those in subcutaneous abdominal ( r = 0.60, P = 0.008), intra-abdominal ( r = 0.75, P = 0.0001) and liver ( r = 0.49, P = 0.048) fat. Intrapair differences in whole body insulin sensitivity correlated with those in subcutaneous abdominal ( r = −0.72, P = 0.001) and intra-abdominal ( r = −0.55, P = 0.015) but not liver ( r = −0.20, P = 0.20) fat. We conclude that acquired obesity is associated with increases in intra-abdominal and liver fat and insulin resistance, independent of genetic factors.

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Effect of Exercise Training on Fat Loss—Energetic Perspectives and the Role of Improved Adipose Tissue Function and Body Fat Distribution

Frontiers in Physiology ◽

10.3389/fphys.2021.737709 ◽

2021 ◽

Vol 12 ◽

Author(s):

Kristoffer Jensen Kolnes ◽

Maria Houborg Petersen ◽

Teodor Lien-Iversen ◽

Kurt Højlund ◽

Jørgen Jensen

Keyword(s):

Physical Activity ◽

Weight Loss ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

Exercise Training ◽

Cardiorespiratory Fitness ◽

Body Fat ◽

Interval Training ◽

Fat Distribution ◽

Abdominal Fat

In obesity, excessive abdominal fat, especially the accumulation of visceral adipose tissue (VAT), increases the risk of metabolic disorders, such as type 2 diabetes mellitus (T2DM), cardiovascular disease, and non-alcoholic fatty liver disease. Excessive abdominal fat is associated with adipose tissue dysfunction, leading to systemic low-grade inflammation, fat overflow, ectopic lipid deposition, and reduced insulin sensitivity. Physical activity is recommended for primary prevention and treatment of obesity, T2DM, and related disorders. Achieving a stable reduction in body weight with exercise training alone has not shown promising effects on a population level. Because fat has a high energy content, a large amount of exercise training is required to achieve weight loss. However, even when there is no weight loss, exercise training is an effective method of improving body composition (increased muscle mass and reduced fat) as well as increasing insulin sensitivity and cardiorespiratory fitness. Compared with traditional low-to-moderate-intensity continuous endurance training, high-intensity interval training (HIIT) and sprint interval training (SIT) are more time-efficient as exercise regimens and produce comparable results in reducing total fat mass, as well as improving cardiorespiratory fitness and insulin sensitivity. During high-intensity exercise, carbohydrates are the main source of energy, whereas, with low-intensity exercise, fat becomes the predominant energy source. These observations imply that HIIT and SIT can reduce fat mass during bouts of exercise despite being associated with lower levels of fat oxidation. In this review, we explore the effects of different types of exercise training on energy expenditure and substrate oxidation during physical activity, and discuss the potential effects of exercise training on adipose tissue function and body fat distribution.

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CTRP12 ablation differentially affects energy expenditure, body weight, and insulin sensitivity in male and female mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00533.2019 ◽

2020 ◽

Vol 319 (1) ◽

pp. E146-E162 ◽

Cited By ~ 2

Author(s):

Stefanie Y. Tan ◽

Xia Lei ◽

Hannah C. Little ◽

Susana Rodriguez ◽

Dylan C. Sarver ◽

...

Keyword(s):

Body Weight ◽

Weight Gain ◽

Insulin Sensitivity ◽

Energy Expenditure ◽

Elevated Serum ◽

Liver Weight ◽

Homozygous Deletion ◽

Whole Body ◽

Male Mice ◽

Female Mice

Secreted hormones facilitate tissue cross talk to maintain energy balance. We previously described C1q/TNF-related protein 12 (CTRP12) as a novel metabolic hormone. Gain-of-function and partial-deficiency mouse models have highlighted important roles for this fat-derived adipokine in modulating systemic metabolism. Whether CTRP12 is essential and required for metabolic homeostasis is unknown. We show here that homozygous deletion of Ctrp12 gene results in sexually dimorphic phenotypes. Under basal conditions, complete loss of CTRP12 had little impact on male mice, whereas it decreased body weight (driven by reduced lean mass and liver weight) and improved insulin sensitivity in female mice. When challenged with a high-fat diet, Ctrp12 knockout (KO) male mice had decreased energy expenditure, increased weight gain and adiposity, elevated serum TNFα level, and reduced insulin sensitivity. In contrast, female KO mice had reduced weight gain and liver weight. The expression of lipid synthesis and catabolism genes, as well as profibrotic, endoplasmic reticulum stress, and oxidative stress genes were largely unaffected in the adipose tissue of Ctrp12 KO male mice. Despite greater adiposity and insulin resistance, Ctrp12 KO male mice fed an obesogenic diet had lower circulating triglyceride and free fatty acid levels. In contrast, lipid profiles of the leaner female KO mice were not different from those of WT controls. These data suggest that CTRP12 contributes to whole body energy metabolism in genotype-, diet-, and sex-dependent manners, underscoring complex gene-environment interactions influencing metabolic outcomes.

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