The Impact of Exercise Training Compared to Caloric Restriction on Hepatic and Peripheral Insulin Resistance in Obesity

John O. Holloszy, as perhaps the world’s preeminent exercise biochemist/physiologist, published >400 papers over his 50+ year career, and they have been cited >41,000 times. In 1965 Holloszy showed for the first time that exercise training in rodents resulted in a doubling of skeletal muscle mitochondria, ushering in a very active era of skeletal muscle plasticity research. He subsequently went on to describe the consequences of and the mechanisms underlying these adaptations. Holloszy was first to show that muscle contractions increase muscle glucose transport independent of insulin, and he studied the mechanisms underlying this response throughout his career. He published important papers assessing the impact of training on glucose and insulin metabolism in healthy and diseased humans. Holloszy was at the forefront of rodent studies of caloric restriction and longevity in the 1980s, following these studies with important cross-sectional and longitudinal caloric restriction studies in humans. Holloszy was influential in the discipline of cardiovascular physiology, showing that older healthy and diseased populations could still elicit beneficial cardiovascular adaptations with exercise training. Holloszy and his group made important contributions to exercise physiology on the effects of training on numerous metabolic, hormonal, and cardiovascular adaptations. Holloszy’s outstanding productivity was made possible by his mentoring of ~100 postdoctoral fellows and substantial NIH grant funding over his entire career. Many of these fellows have also played critical roles in the exercise physiology/biochemistry discipline. Thus it is clear that exercise biochemistry and physiology will be influenced by John Holloszy for numerous years to come.

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Exercise and insulin resistance in PCOS: muscle insulin signalling and fibrosis

Endocrine Connections ◽

10.1530/ec-19-0551 ◽

2020 ◽

Vol 9 (4) ◽

pp. 346-359 ◽

Cited By ~ 3

Author(s):

N K Stepto ◽

D Hiam ◽

M Gibson-Helm ◽

S Cassar ◽

C L Harrison ◽

...

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Exercise Training ◽

Aerobic Exercise ◽

Transforming Growth Factor ◽

Insulin Signalling ◽

Tissue Fibrosis ◽

Overweight Women ◽

The Impact ◽

Specific Insulin

Objective Mechanisms of insulin resistance in polycystic ovary syndrome (PCOS) remain ill defined, contributing to sub-optimal therapies. Recognising skeletal muscle plays a key role in glucose homeostasis we investigated early insulin signalling, its association with aberrant transforming growth factor β (TGFβ)-regulated tissue fibrosis. We also explored the impact of aerobic exercise on these molecular pathways. Methods A secondary analysis from a cross-sectional study was undertaken in women with (n = 30) or without (n = 29) PCOS across lean and overweight BMIs. A subset of participants with (n = 8) or without (n = 8) PCOS who were overweight completed 12 weeks of aerobic exercise training. Muscle was sampled before and 30 min into a euglycaemic-hyperinsulinaemic clamp pre and post training. Results We found reduced signalling in PCOS of mechanistic target of rapamycin (mTOR). Exercise training augmented but did not completely rescue this signalling defect in women with PCOS. Genes in the TGFβ signalling network were upregulated in skeletal muscle in the overweight women with PCOS but were unresponsive to exercise training except for genes encoding LOX, collagen 1 and 3. Conclusions We provide new insights into defects in early insulin signalling, tissue fibrosis, and hyperandrogenism in PCOS-specific insulin resistance in lean and overweight women. PCOS-specific insulin signalling defects were isolated to mTOR, while gene expression implicated TGFβ ligand regulating a fibrosis in the PCOS-obesity synergy in insulin resistance and altered responses to exercise. Interestingly, there was little evidence for hyperandrogenism as a mechanism for insulin resistance.

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Pathophysiological Features of Obesity and its Impact on Cognition: Exercise Training as a Non-Pharmacological Approach

Current Pharmaceutical Design ◽

10.2174/1381612826666200114102524 ◽

2020 ◽

Vol 26 (9) ◽

pp. 916-931 ◽

Cited By ~ 2

Author(s):

Daniela S. Inoue ◽

Bárbara M. Antunes ◽

Mohammad F.B. Maideen ◽

Fábio S. Lira

Keyword(s):

Insulin Resistance ◽

Exercise Training ◽

Cognitive Performance ◽

Physically Active ◽

Health Maintenance ◽

Pharmacological Approach ◽

Cognitive Components ◽

Resistance Reduction ◽

Inflammatory Profile ◽

The Impact

Background: The number of individuals with obesity is growing worldwide and this is a worrying trend, as obesity has shown to cause pathophysiological changes, which result in the emergence of comorbidities such as cardiovascular disease, diabetes mellitus type 2 and cancer. In addition, cognitive performance may be compromised by immunometabolic deregulation of obesity. Although in more critical cases, the use of medications is recommended, a physically active lifestyle is one of the main foundations for health maintenance, making physical training an important tool to reduce the harmful effects of excessive fat accumulation. Aim: The purpose of this review of the literature is to present the impact of immunometabolic alterations on cognitive function in individuals with obesity, and the role of exercise training as a non-pharmacological approach to improve the inflammatory profile, energy metabolism and neuroplasticity in obesity. Method: An overview of the etiology and pathophysiology of obesity to establish a possible link with cognitive performance in obese individuals, with the executive function being one of the most affected cognitive components. In addition, the brain-derived neurotrophic factor (BDNF) profile and its impact on cognition in obese individuals are discussed. Lastly, studies showing regular resistance and/or aerobic training, which may be able to improve the pathophysiological condition and cognitive performance through the improvement of the inflammatory profile, decreased insulin resistance and higher BDNF production are discussed. Conclusion: Exercise training is essential for reestablishment and maintenance of health by increasing energy expenditure, insulin resistance reduction, anti-inflammatory proteins and neurotrophin production corroborating to upregulation of body function.

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Preventive effects of exercise training on dexamethasone‐induced hypertension, oxidative stress and peripheral insulin resistance

The FASEB Journal ◽

10.1096/fasebj.24.1_supplement.982.7 ◽

2010 ◽

Vol 24 (S1) ◽

Author(s):

Sandra Lia Amaral ◽

Otavio Andre Brogin Perez ◽

Matheus Barel ◽

Luiz Roberto Bechara ◽

Leonardo Y Tanaka ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Exercise Training ◽

Peripheral Insulin Resistance ◽

Induced Hypertension ◽

Preventive Effects

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Effects of exercise training and diet on lipid kinetics during free fatty acid-induced insulin resistance in older obese humans with impaired glucose tolerance

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00220.2009 ◽

2009 ◽

Vol 297 (2) ◽

pp. E552-E559 ◽

Cited By ~ 35

Author(s):

Thomas P. J. Solomon ◽

Jacob M. Haus ◽

Christine M. Marchetti ◽

William C. Stanley ◽

John P. Kirwan

Keyword(s):

Insulin Resistance ◽

Weight Loss ◽

Exercise Training ◽

Glucose Tolerance ◽

Impaired Glucose Tolerance ◽

Cellular Level ◽

Whole Body ◽

Heparin Infusion ◽

Peripheral Insulin Resistance ◽

Exercise Induced

Elevated free fatty acids (FFA) are implicated with insulin resistance at the cellular level. However, the contribution of whole body lipid kinetics to FFA-induced insulin resistance is not well understood, and the effect of exercise and diet on this metabolic defect is not known. We investigated the effect of 12 wk of exercise training with and without caloric restriction on FFA turnover and oxidation (FFAox) during acute FFA-induced insulin resistance. Sixteen obese subjects with impaired glucose tolerance were randomized to either a hypocaloric ( n = 8; −598 ± 125 kcal/day, 66 ± 1 yr, 32.8 ± 1.8 kg/m2) or a eucaloric ( n = 8; 67 ± 2 yr, 35.3 ± 2.1 kg/m2) diet and aerobic exercise (1 h/day at 65% of maximal oxygen uptake) regimen. Lipid kinetics ([1-14C]palmitate) were assessed throughout a 7-h, 40 mU·m−2·min−1 hyperinsulinemic euglycemic clamp, during which insulin resistance was induced in the last 5 h by a sustained elevation in plasma FFA (intralipid/heparin infusion). Despite greater weight loss in the hypocaloric group (−7.7 ± 0.5 vs. −3.3 ± 0.7%, P < 0.001), FFA-induced peripheral insulin resistance was improved equally in both groups. However, circulating FFA concentrations (2,123 ± 261 vs. 1,764 ± 194 μmol/l, P < 0.05) and FFA turnover (3.20 ± 0.58 vs. 2.19 ± 0.58 μmol·kg FFM−1·min−1, P < 0.01) during hyperlipemia were suppressed only in the hypocaloric group. In contrast, whole body FFAox was improved in both groups at rest and during hyperlipemia. These changes were driven by increases in intracellular lipid-derived FFAox (12.3 ± 7.7 and 14.7 ± 7.8%, P < 0.05). We conclude that the exercise-induced improvement in FFA-induced insulin resistance is independent of the magnitude of weight loss and FFA turnover, yet it is linked to increased intracellular FFA utilization.

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