Sex differences in drug addiction and response to exercise intervention: From human to animal studies

Obesity is a major risk factor for metabolic disease. Growth differentiation factor 15 (GDF15) has shown promise as a weight loss agent for obesity in animal studies. In healthy lean humans, fasting plasma GDF15 increases after acute exercise. However, the role of GDF15 in human obesity and the response of plasma GDF15 to exercise training in patients with obesity is unknown. Here, 24 sedentary volunteers with obesity [age: 65 ± 1 yr; body mass index (BMI): 35.3 ± 0.9 kg/m2] participated in a supervised 12-wk aerobic exercise intervention: 1 h/day, 5 days/wk at ~85% maximum heart rate with controlled isocaloric diet. As a result, plasma GDF15 was significantly increased (PRE: 644.1 ± 42.6 pg/ml, POST: 704.4 ± 47.2 pg/ml, P < 0.01) after the exercise intervention. Inconsistent with animal models, ΔGDF15 was not correlated with change in weight, BMI, or resting energy expenditure. However, ΔGDF15 was correlated with a reduction in total fat mass ( P < 0.05), abdominal fat mass ( P < 0.05), and android fat mass ( P ≤ 0.05). Participants with a positive GDF15 response to exercise had increased total fat oxidation (PRE: 0.25 ± 0.05 mg·kg−1·min−1, POST: 0.43 ± 0.07 mg·kg−1·min−1, P ≤ 0.05), metabolic flexibility [PRE: −0.01 ± 0.01 delta respiratory quotient (RQ), POST: 0.06 ± 0.01 delta RQ, P < 0.001], and insulin sensitivity (PRE: 0.33 ± 0.01 QUICKI index, POST: 0.34 ± 0.01 QUICKI index, P < 0.01), suggesting a link between GDF15 and fat mass loss as well as exercise-induced metabolic improvement in humans with obesity. We conclude that the exercise-induced increase in plasma GDF15 and the association with reduced fat mass may indicate a role for GDF15 as a therapeutic target for human obesity.

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Sex differences in exercise and drug addiction: A mini review of animal studies

Journal of Sport and Health Science ◽

10.1016/j.jshs.2014.04.005 ◽

2014 ◽

Vol 3 (3) ◽

pp. 163-169 ◽

Cited By ~ 8

Author(s):

Yuehui Zhou ◽

Chenglin Zhou ◽

Rena Li

Keyword(s):

Sex Differences ◽

Drug Addiction ◽

Animal Studies

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Impulsivity and Drug Addiction: A Neurobiological Perspective

10.1093/oxfordhb/9780195389715.013.0078 ◽

2012 ◽

Author(s):

Trevor Robbins

Keyword(s):

Drug Addiction ◽

Conceptual Analysis ◽

Animal Studies ◽

Reaction Time Task ◽

Compulsive Behavior ◽

Self Administration ◽

Detailed Characterization ◽

Cocaine Seeking ◽

Serial Reaction

A conceptual analysis of the impulsivity construct in behavioral and neurobiological terms is followed by an analysis of its causal role in certain forms of drug addiction in both human and animal studies. The main focus of this chapter is on a rat model of impulsivity based on premature responding in the five-choice serial reaction time task and a more detailed characterization of this phenotype in neurobehavioral, neurochemical, and genetic terms. Evidence is surveyed that high impulsivity on this task is associated with the escalation subsequently of cocaine self-administration behavior and also with a tendency toward compulsive cocaine seeking. Novelty reactivity, by contrast, is associated with the enhanced acquisition of self-administration, but not with the escalation of intravenous self-administration of cocaine or the development of compulsive behavior associated with cocaine seeking. These results indicate that the vulnerability to stimulant addiction may depend on different factors, as expressed through distinct presumed endophenotypes. These observations help us further to dissociate various aspects of the impulsivity construct in neural as well as behavioral terms.

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Less pronounced response to exercise in healthy relatives to type 2 diabetic subjects compared with controls

Journal of Applied Physiology ◽

10.1152/japplphysiol.01067.2014 ◽

2015 ◽

Vol 119 (9) ◽

pp. 953-960 ◽

Cited By ~ 9

Author(s):

C. Ekman ◽

T. Elgzyri ◽

K. Ström ◽

P. Almgren ◽

H. Parikh ◽

...

Keyword(s):

Type 2 Diabetes ◽

Body Mass Index ◽

Waist Circumference ◽

Body Mass ◽

Exercise Intervention ◽

Peak Oxygen Consumption ◽

Cellular Respiration ◽

Muscle Adaptation ◽

Response To Exercise

Healthy first-degree relatives with heredity of type 2 diabetes (FH+) are known to have metabolic inflexibility compared with subjects without heredity for diabetes (FH−). In this study, we aimed to test the hypothesis that FH+ individuals have an impaired response to exercise compared with FH−. Sixteen FH+ and 19 FH− insulin-sensitive men similar in age, peak oxygen consumption (V̇o2 peak), and body mass index completed an exercise intervention with heart rate monitored during exercise for 7 mo. Before and after the exercise intervention, the participants underwent a physical examination and tests for glucose tolerance and exercise capacity, and muscle biopsies were taken for expression analysis. The participants attended, on average, 39 training sessions during the intervention and spent 18.8 MJ on exercise. V̇o2 peak/kg increased by 14%, and the participants lost 1.2 kg of weight and 3 cm waist circumference. Given that the FH+ group expended 61% more energy during the intervention, we used regression analysis to analyze the response in the FH+ and FH− groups separately. Exercise volume had a significant effect on V̇o2 peak, weight, and waist circumference in the FH− group, but not in the FH+ group. After exercise, expression of genes involved in metabolism, oxidative phosphorylation, and cellular respiration increased more in the FH− compared with the FH+ group. This suggests that healthy, insulin-sensitive FH+ and FH− participants with similar age, V̇o2 peak, and body mass index may respond differently to an exercise intervention. The FH+ background might limit muscle adaptation to exercise, which may contribute to the increased susceptibility to type 2 diabetes in FH+ individuals.

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Behavioral interventions to benefit cognition (Intervenciones cognitivas para beneficiar la cognición)

Retos ◽

10.47197/retos.v0i27.34377 ◽

2015 ◽

pp. 197-202

Author(s):

Jennifer L. Etnier ◽

Chia-Hao Shih ◽

Aaron Piepmeier

Keyword(s):

Cognitive Function ◽

Cognitive Decline ◽

Behavioral Interventions ◽

Animal Studies ◽

Exercise Intervention ◽

Treatment Strategies ◽

Future Research ◽

Dietary Interventions ◽

Cross Sectional ◽

Age Related

With the growing population of older adults, the identification of treatment strategies to prevent or ameliorate age-related cognitive decline has been an important topic in recent years. After reviewing cross-sectional, longitudinal, and experimentally designed studies, as well as evidence from narrative and meta-analytic reviews, the authors concluded that behavioral approaches such as physical activity, cognitive training, and dietary interventions show promising results. In addition, given the likelihood that multiple underlying mechanisms support cognitive function, research is currently focusing on how to combine lifestyle factors into multi-component interventions to generate greater and more meaningful effects. Though evidence for these enhanced benefits exists from animal studies, few multi-component studies have been performed with humans. However, the findings from these studies are promising and a continued pursuit of multi-component behavioral interventions to benefit cognitive performance is warranted. Given the world’s aging population and accompanying age-related health issues such as cognitive decline and dementia, future research should focus on understanding the biological mechanisms responsible for these effects in order to allow for the development of behavioral lifestyle prescriptions to benefit cognitive performance.Keywords. aging, cognitive function, exercise intervention, oxidative stress, cognitive engagement.Resumen. Con la creciente población de adultos mayores, la identificación de las estrategias de tratamiento para prevenir o mejorar el deterioro cognitivo relacionado con la edad ha sido un tema importante en los últimos años. Después de revisar estudios con diseños transversales, longitudinales y experimentales, así como la evidencia de revisiones de literatura narrativa y meta-analítica, los autores concluyen que los enfoques conductuales como la actividad física, el entrenamiento cognitivo y las intervenciones dietéticas muestran resultados prometedores. Además, dada la probabilidad de que múltiples mecanismos subyacentes apoyan la función cognitiva, las investigaciones se enfocan actualmente en la manera de cómo combinar factores del estilo de vida en las intervenciones con múltiples componentes para generar efectos mayores y más significativos. Aunque existe evidencia de estos beneficios a partir de estudios en animales, se han realizado pocos estudios de componentes múltiples en humanos. Sin embargo, los resultados de estos estudios son prometedores y se garantiza un seguimiento continuo de las intervenciones conductuales de componentes múltiples para beneficiar el rendimiento cognitivo. Teniendo en cuenta el envejecimiento de la población mundial y los problemas de salud relacionados con la edad que la acompañan, tales como el deterioro cognitivo y la demencia, la investigación futura debería centrarse en la comprensión de los mecanismos biológicos responsables de estos efectos con el fin de permitir el desarrollo de las prescripciones de comportamiento de estilo de vida para beneficiar el rendimiento cognitivo.Palabras claves. envejecimiento, funcionamiento cognitivo, intervención con ejercicio, estrés oxidativo, participación cognitiva.

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Substance use disorders and the mechanisms of drug addiction

New Oxford Textbook of Psychiatry ◽

10.1093/med/9780198713005.003.0048 ◽

2020 ◽

pp. 477-491

Author(s):

Trevor W. Robbins ◽

Barry J. Everitt

Keyword(s):

Drug Addiction ◽

Positive Reinforcement ◽

Animal Studies ◽

Dorsal Striatum ◽

Critical Issue ◽

Neural Substrates ◽

Future Prospects ◽

Self Administration ◽

Limbic Systems ◽

Brain Changes

The understanding of drug addiction has gained much from a neuroscientific approach, reflected by changing approaches in diagnosis. The two main psychological accounts of addiction to substances, ranging from alcohol and nicotine to opioids and stimulant drugs, are opponent motivational processing, emphasizing the importance of withdrawal symptoms, and aberrant learning from positive reinforcement. The neural and neurochemical systems implicated have been identified on the basis of animal studies, using especially the self-administration paradigm, and human investigations employing a range of brain imaging modalities. These neural substrates include dopamine-dependent functions of the ventral and dorsal striatum, as well as regulatory influences of fronto-limbic systems. The chapter considers the critical issue of cause and effect, and whether brain changes reflect neurotoxic effects of abuse or whether there are predisposing neurobehavioural factors. It also outlines the current situation and future prospects for treatment by medication, possibly in association with psychological approaches.

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Towards a personalised approach in exercise-based cardiovascular rehabilitation: How can translational research help? A ‘call to action’ from the Section on Secondary Prevention and Cardiac Rehabilitation of the European Association of Preventive Cardiology

European Journal of Preventive Cardiology ◽

10.1177/2047487319877716 ◽

2019 ◽

Vol 27 (13) ◽

pp. 1369-1385 ◽

Cited By ~ 9

Author(s):

Andreas B Gevaert ◽

Volker Adams ◽

Martin Bahls ◽

T Scott Bowen ◽

Veronique Cornelissen ◽

...

Keyword(s):

Translational Research ◽

Molecular Mechanisms ◽

Exercise Intervention ◽

Metabolic Diseases ◽

Position Paper ◽

Holistic View ◽

Call To Action ◽

Preventive Cardiology ◽

Cardiovascular Rehabilitation ◽

Response To Exercise

The benefit of regular physical activity and exercise training for the prevention of cardiovascular and metabolic diseases is undisputed. Many molecular mechanisms mediating exercise effects have been deciphered. Personalised exercise prescription can help patients in achieving their individual greatest benefit from an exercise-based cardiovascular rehabilitation programme. Yet, we still struggle to provide truly personalised exercise prescriptions to our patients. In this position paper, we address novel basic and translational research concepts that can help us understand the principles underlying the inter-individual differences in the response to exercise, and identify early on who would most likely benefit from which exercise intervention. This includes hereditary, non-hereditary and sex-specific concepts. Recent insights have helped us to take on a more holistic view, integrating exercise-mediated molecular mechanisms with those influenced by metabolism and immunity. Unfortunately, while the outline is recognisable, many details are still lacking to turn the understanding of a concept into a roadmap ready to be used in clinical routine. This position paper therefore also investigates perspectives on how the advent of ‘big data’ and the use of animal models could help unravel inter-individual responses to exercise parameters and thus influence hypothesis-building for translational research in exercise-based cardiovascular rehabilitation.

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Resveratrol modulates the angiogenic response to exercise training in skeletal muscles of aged men

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00168.2014 ◽

2014 ◽

Vol 307 (8) ◽

pp. H1111-H1119 ◽

Cited By ~ 25

Author(s):

Lasse Gliemann ◽

Jesper Olesen ◽

Rasmus Sjørup Biensø ◽

Jakob Friis Schmidt ◽

Thorbjorn Akerstrom ◽

...

Keyword(s):

Exercise Training ◽

Animal Studies ◽

Muscle Protein ◽

Daily Intake ◽

Training Group ◽

Treated Group ◽

Vegf Receptor ◽

Protein Levels ◽

Angiogenic Effect ◽

Response To Exercise

In animal studies, the polyphenol resveratrol has been shown to influence several pathways of importance for angiogenesis in skeletal muscle. The aim of the present study was to examine the angiogenic effect of resveratrol supplementation with parallel exercise training in aged men. Forty-three healthy physically inactive aged men (65 ± 1 yr) were divided into 1) a training group that conducted 8 wk of intense exercise training where half of the subjects received a daily intake of either 250 mg trans-resveratrol ( n = 14) and the other half received placebo ( n = 13) and 2) a nontraining group that received either 250 mg trans-resveratrol ( n = 9) or placebo ( n = 7). The group that trained with placebo showed a ∼20% increase in the capillary-to-fiber ratio, an increase in muscle protein expression of VEGF, VEGF receptor-2, and tissue inhibitor of matrix metalloproteinase (TIMP-1) but unaltered thrombospodin-1 levels. Muscle interstitial VEGF and thrombospodin-1 protein levels were unchanged after the training period. The group that trained with resveratrol supplementation did not show an increase in the capillary-to-fiber ratio or an increase in muscle VEGF protein. Muscle TIMP-1 protein levels were lower in the training and resveratrol group than in the training and placebo group. Both training groups showed an increase in forkhead box O1 protein. In nontraining groups, TIMP-1 protein was lower in the resveratrol-treated group than the placebo-treated group after 8 wk. In conclusion, these data show that exercise training has a strong angiogenic effect, whereas resveratrol supplementation may limit basal and training-induced angiogenesis.

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Sex and gender differences in hypertensive kidney injury

AJP Renal Physiology ◽

10.1152/ajprenal.00206.2017 ◽

2017 ◽

Vol 313 (4) ◽

pp. F1009-F1017 ◽

Cited By ~ 18

Author(s):

Jennifer C. Sullivan ◽

Ellen E. Gillis

Keyword(s):

Sex Differences ◽

Experimental Animal ◽

Animal Studies ◽

Molecular Mechanisms ◽

Kidney Injury ◽

Science Research ◽

The United States ◽

Sex And Gender ◽

Participation Of Women ◽

And Gender

Hypertension is a complex, multifaceted disorder, affecting ~1 in 3 adults in the United States. Although hypertension occurs in both men and women, there are distinct sex differences in the way in which they develop hypertension, with women having a lower incidence of hypertension until the sixth decade of life. Despite observed sex differences in hypertension, little is known about the molecular mechanisms underlying the development of hypertension in females, primarily because of their underrepresentation in both clinical and experimental animal studies. The first goal of this review is to provide a concise overview of the participation of women in clinical trials, including a discussion of the importance of including females in basic science research, as recently mandated by the National Institutes of Health. The remaining portion of the review is dedicated to identifying clinical and experimental animal studies that concentrate on gender and sex differences in hypertensive kidney disease, ending with a proposed role for T cells in mediating sex differences in blood pressure.

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Sex differences in the neurobiology of drug addiction

Experimental Neurology ◽

10.1016/j.expneurol.2014.01.022 ◽

2014 ◽

Vol 259 ◽

pp. 64-74 ◽

Cited By ~ 107

Author(s):

Samara A.M. Bobzean ◽

Aliza K. DeNobrega ◽

Linda I. Perrotti

Keyword(s):

Sex Differences ◽

Drug Addiction

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