Voluntary wheel running ameliorates vascular smooth muscle hyper-contractility in type 2 diabetic db/db mice

2007 ◽  
Vol 32 (4) ◽  
pp. 711-720 ◽  
Author(s):  
Karyn A. Esser ◽  
Wen Su ◽  
Sergey Matveev ◽  
Vicki Wong ◽  
Li Zeng ◽  
...  
Keyword(s):  
Physical Activity ◽  
Smooth Muscle ◽  
Blood Glucose ◽  
Vascular Smooth Muscle ◽  
Wheel Running ◽  
Voluntary Wheel Running ◽  
Voluntary Physical Activity ◽  
Type 2 Diabetic ◽  
Voluntary Wheel

Physical activity reduces cardiovascular disease related mortality in diabetic patients. However, it is unknown if the diabetic state reduces voluntary physical activity and, if so, if the voluntary physical activity at the reduced level is sufficient to improve cardiovascular risk factors. To address these two specific questions, we investigated voluntary wheel running performance in an obese and type 2 diabetic mouse model, the db/db mice. In addition, we determined the effects of running on body mass, blood glucose, insulin, plasma free fatty acids, cholesterol, and vascular smooth muscle hyper-contractility. Our results showed that daily running distance, time, and speed were significantly reduced in the db/db mice to about 23%, 32%, and 71%, respectively, of that in non-diabetic control mice. However, this low level of running was sufficient to induce a reduction in the vascular smooth muscle hyper-contractility, cholesterol, and some plasma free fatty acids, as well as to delay the decrease in blood insulin. These changes occurred in the absence of weight loss and a detectable decrease in blood glucose. Thus, the results of this study demonstrated that voluntary wheel running activity was dramatically reduced in db/db mice. However, the low levels of running were beneficial, in the absence of effects on obesity or blood glucose, with significant reductions in cardiovascular risk factors and potential delays in β-cell dysfunction.

scholarly journals Voluntary Wheel Running Ameliorates Vascular Smooth Muscle Hyper‐contractility in Type 2 Diabetic db/db Mice

2007 ◽  
Vol 21 (5) ◽  
Author(s):  
Karyn A. Esser ◽  
Wen Su ◽  
Sergey Matveev ◽  
Vicki Wong ◽  
Li Zeng ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Wheel Running ◽  
Voluntary Wheel Running ◽  
Type 2 Diabetic ◽  
Voluntary Wheel

scholarly journals Examination of nucleus accumbens mechanisms underlying the motivation for physical activity

2017 ◽  
Author(s):  
◽  
Gregory Neal Ruegsegger
Keyword(s):  
Physical Activity ◽  
Nucleus Accumbens ◽  
Molecular Mechanisms ◽  
Leptin Receptor ◽  
Wheel Running ◽  
Receptor Expression ◽  
Voluntary Wheel Running ◽  
Age Related ◽  
Voluntary Physical Activity ◽  
Voluntary Wheel

Physical inactivity, a primary contributor to numerous diseases including obesity, type 2 diabetes, depression, and dementia, has reached pandemic levels worldwide. Alarmingly, the percentage of individuals engaging in physical activity is low and decreasing. Accelerometry data shows that > 90% of adults fail to meet the U.S. Physical Activity Guidelines despite the excess of knowledge suggesting exercise improves health. Therefore, beginning to understand the molecular mechanisms which influence physical activity levels is imperative for the development of therapies to reduce sedentary behavior. The work presented in this dissertation made use of three independent experimental paradigms in rats to test the hypothesis that differences in the mesolimbic dopamine system associate with/cause changes in voluntary physical activity. In the first study, rats selectively bred for high (HVR) or low (LVR) voluntary wheel running distance were used to assess inherent differences in opioidergic signaling between HVR and LVR, as well as the influence of dopamine on opioid-induced changes in voluntary wheel running. Mu-opioid receptor expression and function was increased in the nucleus accumbens (NAc) of HVR compared to LVR. Likewise, naltrexone injection decreased dopamine-related mRNA expression in mesolimbic brain regions and reduced wheel running in HVR, but not LVR. Finally, lesion of dopaminergic neurons in the NAc prevented the decrease in running following naltrexone administration in HVR, suggesting opioidergic signaling requires downstream dopaminergic activity to influence voluntary running. In the second study, the transgenerational effect of maternal Western diet (WD) on offspring voluntary wheel running was assessed. Wheel running was increased in female WD offspring from 4-7 weeks of age, but decreased running from 16-19 weeks of age, compared to offspring from chow fed dams. These age-specific changes in wheel running are associated with the up- and down-regulation of dopamine receptor 1 in the NAc at 6 and 18 weeks of age, respectively, in WD female offspring, which in turn was negatively associated with leptin receptor mRNA in the ventral tegmental area. In the third study, age-related influences on wheel running were assessed in 8 and 14 week-old rats. In addition to a [about]60% reduction in running, RNA-sequencing revealed down-regulations in networks related to cAMP-mediated signaling and synaptic plasticity in the NAc from 8 to 14 weeks-old. The down-regulations of these networks was mirrored by reductions in dendritic spine density in the NAc from 8 to 14 weeks-old. Additionally, intra-NAc injection of the Cdk5 inhibitor roscovitine, a known modulator of dendritic density and dopamine signaling, dose-dependently decreased wheel running. Despite the varying experimental models used in this dissertation, these findings collectively suggest that alterations in dopaminergic signaling in the NAc associate with, and influence, voluntary physical activity.

Inhibition of cell cycle progression and migration of vascular smooth muscle cells by prostaglandin D2 synthase: resistance in diabetic Goto-Kakizaki rats

2004 ◽  
Vol 287 (5) ◽  
pp. C1273-C1281 ◽  
Author(s):  
Louis Ragolia ◽  
Thomas Palaia ◽  
Tara B. Koutrouby ◽  
John K. Maesaka
Keyword(s):  
Cell Cycle ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Cell Cycle Progression ◽  
Fold Increase ◽  
Wild Type ◽  
Cycle Progression ◽  
And Migration ◽  
Type 2 Diabetic

The regulation of vascular smooth muscle cell (VSMC) proliferation, migration, and apoptosis plays a clear role in the atherosclerotic process. Recently, we reported on the inhibition of the exaggerated growth phenotype of VSMCs isolated from hypertensive rats by lipocalin-type prostaglandin D2 synthase (L-PGDS). In the present study, we report the differential effects of L-PGDS on VSMC cell cycle progression, migration, and apoptosis in wild-type VSMCs vs. those from a type 2 diabetic model. In wild-type VSMCs, exogenously added L-PGDS delayed serum-induced cell cycle progression from the G1 to S phase, as determined by gene array analysis and the decreased protein expressions of cyclin-dependent kinase-2, p21Cip1, and cyclin D1. Cyclin D3 protein expression was unaffected by L-PGDS, although its gene expression was stimulated by L-PGDS in wild-type cells. In addition, platelet-derived growth factor-induced VSMC migration was inhibited by L-PGDS in wild-type cells. Type 2 diabetic VSMCs, however, were resistant to the L-PGDS effects on cell cycle progression and migration. L-PGDS did suppress the hyperproliferation of diabetic cells, albeit through a different mechanism, presumably involving the 2.5-fold increase in apoptosis and the concomitant 10-fold increase of L-PGDS uptake we observed in these cells. We propose that in wild-type VSMCs, L-PGDS retards cell cycle progression and migration, precluding hyperplasia of the tunica media, and that diabetic cells appear resistant to the inhibitory effects of L-PGDS, which consequently may help explain the increased atherosclerosis observed in diabetes.

scholarly journals Chronic environmental or genetic elevation of galanin in noradrenergic neurons confers stress resilience in mice

2020 ◽  
Author(s):  
Rachel P. Tillage ◽  
Genevieve E. Wilson ◽  
L. Cameron Liles ◽  
Philip V. Holmes ◽  
David Weinshenker
Keyword(s):  
Physical Activity ◽  
Locus Coeruleus ◽  
Wheel Running ◽  
Neuropsychiatric Disorders ◽  
Noradrenergic Neurons ◽  
Stress Resilience ◽  
Voluntary Wheel Running ◽  
Exercise Induced ◽  
Species Specific ◽  
Voluntary Wheel

ABSTRACTThe neuropeptide galanin has been implicated in stress-related neuropsychiatric disorders in both humans and rodent models. While pharmacological treatments for these disorders are ineffective for many individuals, physical activity is beneficial for stress-related symptoms. Galanin is highly expressed in the noradrenergic system, particularly the locus coeruleus (LC), which is dysregulated in stress-related disorders and activated by exercise. Galanin expression is elevated in the LC by chronic exercise, and blockade of galanin transmission attenuates exercise-induced stress resilience. However, most research on this topic has been done in rats, so it is unclear whether the relationship between exercise and galanin is species-specific. Moreover, use of intracerebroventricular galanin receptor antagonists in prior studies precluded defining a causal role for LC-derived galanin specifically. Therefore, the goals of this study were twofold. First, we investigated whether physical activity (chronic voluntary wheel running) increases stress resilience and galanin expression in the LC of mice. Next, we used transgenic mice that overexpress galanin in noradrenergic neurons (Gal OX) to determine how chronically elevated noradrenergic-derived galanin, alone, alters anxiogenic-like responses to stress. We found that three weeks of ad libitum access to a running wheel in their home cage increased galanin mRNA in the LC of mice and conferred resilience to a stressor. The effects of exercise were phenocopied by galanin overexpression in noradrenergic neurons, and Gal OX mice were resistant to the anxiogenic effect of optogenetic LC activation. Together, these findings support a role for chronically increased noradrenergic galanin in mediating resilience to stress.Significance statementUnderstanding the neurobiological mechanisms underlying behavioral responses to stress is necessary to improve treatments for stress-related neuropsychiatric disorders. Increased physical activity is associated with stress resilience in humans, but the neurobiological mechanisms underlying this effect are not clear. Here we investigate the anxiolytic potential of the neuropeptide galanin from the main noradrenergic nucleus, the locus coeruleus (LC). We show that chronic voluntary wheel running in mice galanin expression in the LC and stress resilience. Furthermore, we show that genetic overexpression of galanin in noradrenergic neurons confers resilience to the anxiogenic effects of foot shock and optogenetic LC activation. These findings support a role for chronically increased noradrenergic galanin in mediating resilience to stress.

Sex dependent effects of physical activity on diet preference in rats selectively bred for high or low levels of voluntary wheel running

2019 ◽  
Vol 359 ◽  
pp. 95-103 ◽  
Author(s):  
Jenna R. Lee ◽  
Melissa A. Tapia ◽  
Jane R. Nelson ◽  
Justin M. Moore ◽  
Graydon B. Gereau ◽  
...  
Keyword(s):  
Physical Activity ◽  
Wheel Running ◽  
Voluntary Wheel Running ◽  
Diet Preference ◽  
Low Levels ◽  
Voluntary Wheel

Voluntary physical activity protects against olanzapine-induced hyperglycemia

2020 ◽  
Author(s):  
Hesham Shamshoum ◽  
Greg Lawrence McKie ◽  
Kyle D. Medak ◽  
Kristin E. Ashworth ◽  
Bruce E. Kemp ◽  
...  
Keyword(s):  
Physical Activity ◽  
Blood Glucose ◽  
Glucose Metabolism ◽  
Wheel Running ◽  
Whole Body ◽  
Light Cycle ◽  
Triglyceride Accumulation ◽  
Insulin Tolerance ◽  
Voluntary Physical Activity ◽  
Running Wheels

Olanzapine (OLZ) is used in the treatment of schizophrenia and a growing number of "off‐label" conditions. While effective in reducing psychoses, OLZ causes rapid impairments in glucose and lipid homeostasis. The purpose of this study was to investigate if voluntary physical activity via wheel running (VWR) would protect against the acute metabolic side effects of OLZ. Male C57BL/6J mice remained sedentary or were provided with running wheels overnight, prior to treatment with OLZ either at the beginning of the light cycle, or 7 or 24 hours following the cessation of VWR. Prior VWR protected against OLZ-induced hyperglycemia immediately and 7 hours following a bout of overnight wheel running. Protection against, hyperglycemia immediately following VWR was associated with increased insulin tolerance and an attenuated OLZ-induced increase in the serum glucagon:insulin ratio. The protective effect of VWR against OLZ-induced increases in hyperglycemia and glucagon:insulin ratio were maintained in high fat fed, and AMPK b1 deficient mice, models which display a potentiated OLZ-induced increase in blood glucose. Repeated OLZ treatment did not impair VWR performance and protection against the acute effects of OLZ on blood glucose was present after 1 week of daily OLZ treatment in mice given access to running wheels. In contrast to the effects on glucose metabolism, VWR, for the most part, did not impact OLZ induced perturbations in lipolysis, liver triglyceride accumulation or whole-body substrate oxidation. Collectively our findings demonstrate the efficacy of voluntary physical activity as an approach to protect against OLZ-induced impairments in glucose metabolism.

scholarly journals Interrelationship of CB1R and OBR pathways in regulation of metabolic, neuroendocrine, and behavioral responses to food restriction and voluntary wheel running

2014 ◽  
Vol 117 (2) ◽  
pp. 97-104 ◽  
Author(s):  
Abdoulaye Diane ◽  
Donna F. Vine ◽  
James C. Russell ◽  
C. Donald Heth ◽  
W. David Pierce ◽  
...  
Keyword(s):  
Physical Activity ◽  
Body Weight ◽  
Food Restriction ◽  
Leptin Receptor ◽  
Wheel Running ◽  
Behavioral Responses ◽  
Voluntary Wheel Running ◽  
Cannabinoid 1 Receptor ◽  
Clinical Measures ◽  
Voluntary Wheel

We hypothesized the cannabinoid-1 receptor and leptin receptor (ObR) operate synergistically to modulate metabolic, neuroendocrine, and behavioral responses of animals exposed to a survival challenge (food restriction and wheel running). Obese-prone (OP) JCR:LA- cp rats, lacking functional ObR, and lean-prone (LP) JCR:LA- cp rats (intact ObR) were assigned to OP-C and LP-C (control) or CBR1-antagonized (SR141716, 10 mg/kg body wt in food) OP-A and LP-A groups. After 32 days, all rats were exposed to 1.5-h daily meals without the drug and 22.5-h voluntary wheel running, a survival challenge that normally culminates in activity-based anorexia (ABA). Rats were removed from the ABA protocol when body weight reached 75% of entry weight (starvation criterion) or after 14 days (survival criterion). LP-A rats starved faster (6.44 ± 0.24 days) than LP-C animals (8.00 ± 0.29 days); all OP rats survived the ABA challenge. LP-A rats lost weight faster than animals in all other groups ( P < 0.001). Consistent with the starvation results, LP-A rats increased the rate of wheel running more rapidly than LP-C rats ( P = 0.001), with no difference in hypothalamic and primary neural reward serotonin levels. In contrast, OP-A rats showed suppression of wheel running compared with the OP-C group ( days 6–14 of ABA challenge, P < 0.001) and decreased hypothalamic and neural reward serotonin levels ( P < 0.01). Thus there is an interrelationship between cannabinoid-1 receptor and ObR pathways in regulation of energy balance and physical activity. Effective clinical measures to prevent and treat a variety of disorders will require understanding of the mechanisms underlying these effects.

P4475Vasodilation- and blood pressure normalization-independent cardioprotective effects of endogenous, physical activity-induced alpha calcitonin gene-related peptide in chronic hypertension

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Skaria ◽  
K Mitchell ◽  
J A Fischer ◽  
W Born ◽  
M Gassmann ◽  
...  
Keyword(s):  
Physical Activity ◽  
Blood Pressure ◽  
Cardiac Tissue ◽  
Wheel Running ◽  
Chronic Hypertension ◽  
Voluntary Wheel Running ◽  
Cardioprotective Effects ◽  
Pressure Independent ◽  
And Function ◽  
Voluntary Wheel

Abstract Background Alpha calcitonin gene-related peptide (αCGRP) is one of the strongest vasodilators and, as such, is cardioprotective in chronic hypertension when reducing the associated elevated blood pressure. However, we hypothesize that endogenous, physical activity-induced αCGRP has blood pressure independent cardioprotective effects in chronic hypertension. Methods Chronic hypertension was induced in WT and αCGRP−/− mice by one-kidney one-clip surgery. Chronic hypertensive WT and αCGRP−/− mice lived sedentarily or performed voluntary wheel running and were treated simultaneously with either vehicle, αCGRP or αCGRP receptor antagonist CGRP8–37. Cardiac function and tissue phenotype were evaluated echocardiographically and by ddPCR, Western blotting and histology, respectively. Results Blood pressure was similar among all hypertensive experimental groups. Endogenous αCGRP limited pathological cardiac remodeling and symptomatic heart failure already in sedentary, chronic hypertensive WT mice. In these mice, voluntary wheel running significantly improved cardiac tissue phenotype and function, that was abolished by CGRP8–37 treatment. In αCGRP−/− mice, αCGRP treatment, in contrast to voluntary wheel running, improved cardiac tissue phenotype and function. Specific inhibition of proliferation and myofibroblast differentiation of primary murine cardiac fibroblasts by αCGRP suggests involvement of these cells in αCGRP-mediated blunting of pathological cardiac remodeling. Conclusion Endogenous, physical activity-induced αCGRP has blood pressure independent cardioprotective effects and is crucial for maintaining cardiac function in chronic hypertension. Consequently, permanently inhibiting endogenous αCGRP signaling, as currently approved for migraine prophylaxis, could endanger hypertensive patients. Acknowledgement/Funding Swiss National Science Foundation, Novartis Foundation for Medical-biological Research

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