Sex-dependent effects of developmental exposure to bisphenol A and ethinyl estradiol on metabolic parameters and voluntary physical activity

Endocrine disrupting chemicals (EDC) have received considerable attention as potential obesogens. Past studies examining obesogenic potential of one widespread EDC, bisphenol A (BPA), have generally focused on metabolic and adipose tissue effects. However, physical inactivity has been proposed to be a leading cause of obesity. A paucity of studies has considered whether EDC, including BPA, affects this behavior. To test whether early exposure to BPA and ethinyl estradiol (EE, estrogen present in birth control pills) results in metabolic and such behavioral disruptions, California mice developmentally exposed to BPA and EE were tested as adults for energy expenditure (indirect calorimetry), body composition (echoMRI) and physical activity (measured by beam breaks and voluntary wheel running). Serum glucose and metabolic hormones were measured. No differences in body weight or food consumption were detected. BPA-exposed females exhibited greater variation in weight than females in control and EE groups. During the dark and light cycles, BPA females exhibited a higher average respiratory quotient than control females, indicative of metabolizing carbohydrates rather than fats. Various assessments of voluntary physical activity in the home cage confirmed that during the dark cycle, BPA and EE-exposed females were significantly less active in this setting than control females. Similar effects were not observed in BPA or EE-exposed males. No significant differences were detected in serum glucose, insulin, adiponectin and leptin concentrations. Results suggest that females developmentally exposed to BPA exhibit decreased motivation to engage in voluntary physical activity and altered metabolism of carbohydrates v. fats, which could have important health implications.

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Voluntary wheel running is effective on suppressing of obesity but not on blood pressure and insulin resistance in female rats fed with high fructose diet

Trakia Journal of Sciences ◽

10.15547/tjs.2021.01.004 ◽

2021 ◽

Vol 19 (1) ◽

pp. 21-28

Author(s):

P. Tayfur ◽

K. Gökçe Tezel ◽

Ö. Barutçu ◽

S. Yılmaz ◽

E. Ö. Özgür ◽

...

Keyword(s):

Physical Activity ◽

Insulin Resistance ◽

Blood Pressure ◽

Body Weight ◽

Weight Gain ◽

Wheel Running ◽

Female Rats ◽

Walking Distance ◽

Voluntary Activity ◽

Voluntary Physical Activity

A fructose-rich diet has been known to cause metabolic syndrome effects such as body weight gain, increased blood pressure, blood lipids and glucose levels. The role of voluntary physical activity in these alterations is not known clearly. The aim of this study was to investigate the possible improving effects of voluntary physical activity in rats that were feeding with a fructose-rich diet. Spraque-Dawley female rats were separated as control (C;n=7), voluntary physical activity (A;n=7), fructose (F;n=7) and fructose+activity (F+A;n=7) groups. A and FA groups were kept in cages with running wheels during six weeks. F and FA groups were fed with adding 20% fructose in drinking water. Body weight was measured weekly and Lee Index was used to determine obesity. At the end of the feeding period serum glucose, insulin and lipid levels were measured by enzymatic method and blood pressure was determined with the tail-cuff method. Daily voluntary walking distance in F+A and A groups were similar during six weeks. Fructose intake induced to increase systolic blood pressure (p=0.001), diastolic blood pressure (p=0.002), glucose (p=0.041), insulin (p=0.001), cholesterol (p=0.001), triglyceride (p=0.001) and liver weight (p=0.035). The voluntary activity was found effective on the decrease of weight gain (p=0.018) however we did not observe a significant effect on blood pressure (p=0.917) and insulin resistance (p=0.565) following the fructose-rich diet. We conclude that voluntary activity has preventive effect on obesity but may not to be effective on increased blood pressure and insulin resistance in female rats which were feeding fructose-rich diet during six weeks.

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

Applied Physiology Nutrition and Metabolism ◽

10.1139/h07-058 ◽

2007 ◽

Vol 32 (4) ◽

pp. 711-720 ◽

Cited By ~ 9

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.

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Degradation of Endocrine Disrupting Chemicals Bisphenol A, Ethinyl Estradiol, and Estradiol during UV Photolysis and Advanced Oxidation Processes

Environmental Science & Technology ◽

10.1021/es035413p ◽

2004 ◽

Vol 38 (20) ◽

pp. 5476-5483 ◽

Cited By ~ 355

Author(s):

Erik J. Rosenfeldt ◽

Karl G. Linden

Keyword(s):

Bisphenol A ◽

Advanced Oxidation Processes ◽

Ethinyl Estradiol ◽

Endocrine Disrupting Chemicals ◽

Advanced Oxidation ◽

Uv Photolysis ◽

Oxidation Processes ◽

Endocrine Disrupting

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Voluntary physical activity protects against olanzapine-induced hyperglycemia

Journal of Applied Physiology ◽

10.1152/japplphysiol.00876.2020 ◽

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.

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Adipose tissue and vascular phenotypic modulation by voluntary physical activity and dietary restriction in obese insulin-resistant OLETF rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00493.2013 ◽

2014 ◽

Vol 306 (8) ◽

pp. R596-R606 ◽

Cited By ~ 26

Author(s):

Jacqueline M. Crissey ◽

Nathan T. Jenkins ◽

Kasey A. Lansford ◽

Pamela K. Thorne ◽

David S. Bayless ◽

...

Keyword(s):

Physical Activity ◽

Insulin Resistance ◽

Adipose Tissue ◽

Body Fat ◽

Immune Cell ◽

Wheel Running ◽

Diet Restriction ◽

Oletf Rats ◽

Markers Of Inflammation ◽

Voluntary Physical Activity

Adipose tissue (AT)-derived cytokines are proposed to contribute to obesity-associated vascular insulin resistance. We tested the hypothesis that voluntary physical activity and diet restriction-induced maintenance of body weight would both result in decreased AT inflammation and concomitant improvements in insulin-stimulated vascular relaxation in the hyperphagic, obese Otsuka Long-Evans Tokushima fatty (OLETF) rat. Rats (aged 12 wk) were randomly assigned to sedentary (SED; n = 10), wheel running (WR; n = 10), or diet restriction (DR; n = 10; fed 70% of SED) for 8 wk. WR and DR rats exhibited markedly lower adiposity (7.1 ± 0.4 and 15.7 ± 1.1% body fat, respectively) relative to SED (27 ± 1.2% body fat), as well as improved blood lipid profiles and systemic markers of insulin resistance. Reduced adiposity in both WR and DR was associated with decreased AT mRNA expression of inflammatory genes (e.g., MCP-1, TNF-α, and IL-6) and markers of immune cell infiltration (e.g., CD8, CD11c, and F4/80). The extent of these effects were most pronounced in visceral AT compared with subcutaneous and periaortic AT. Markers of inflammation in brown AT were upregulated with WR but not DR. In periaortic AT, WR- and DR-induced reductions in expression and secretion of cytokines were accompanied with a more atheroprotective gene expression profile in the adjacent aortic wall. WR, but not DR, resulted in greater insulin-stimulated relaxation in the aorta; an effect that was, in part, mediated by a decrease in insulin-induced endothelin-1 activation in WR aorta. Collectively, we show in OLETF rats that lower adiposity leads to less AT and aortic inflammation, as well as an exercise-specific improvement in insulin-stimulated vasorelaxation.

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Impacts of Bisphenol A and Ethinyl Estradiol on Male and Female CD-1 Mouse Spleen

10.1101/109009 ◽

2017 ◽

Author(s):

Robin B. Gear ◽

Scott M. Belcher

Keyword(s):

Immune System ◽

Bisphenol A ◽

Ethinyl Estradiol ◽

Endocrine Disrupting Chemicals ◽

Wide Spread ◽

Male And Female ◽

Synthetic Chemicals ◽

Endocrine Disrupting ◽

The Impact

ABSTRACTThe endocrine disruptor bisphenol A (BPA) and the pharmaceutical 17α-ethinyl estradiol (EE) are synthetic chemicals with estrogen-like activities. Despite ubiquitous human exposure to BPA, and the wide-spread clinical use of EE as oral contraceptive adjuvant, the impact of these estrogenic endocrine disrupting chemicals (EDCs) on the immune system is unclear. Here we report results of in vivo dose response studies that analyzed the histology and microstructural changes in the spleen of adult male and female CD-1 mice exposed to 4 to 40,000 μg/kg/day BPA or 0.02 to 2 μg/kg/day EE from conception until 12-14 weeks of age. Results of that analysis indicate that both BPA and EE have dose- and sex-specific impacts on the cellular and microanatomical structures of the spleens that reveal minor alterations in immunomodulatory and hematopoietic functions. These findings support previous studies demonstrating the murine immune system as a sensitive target for estrogens, and that oral exposures to BPA and EE can have estrogen-like immunomodulatory affects in both sexes.

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Voluntary physical activity prevents stress-induced behavioral depression and anti-KLH antibody suppression

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2001.281.2.r484 ◽

2001 ◽

Vol 281 (2) ◽

pp. R484-R489 ◽

Cited By ~ 63

Author(s):

Albert Moraska ◽

Monika Fleshner

Keyword(s):

Physical Activity ◽

Home Cage ◽

Wheel Running ◽

Negative Impact ◽

Keyhole Limpet Hemocyanin ◽

Sprague Dawley ◽

Physically Active ◽

Behavioral Depression ◽

Sprague Dawley Rats ◽

Voluntary Physical Activity

The current study addressed whether physical activity can buffer stress-induced “behavioral depression” and immunosuppression. Adult, male Sprague-Dawley rats were housed with either a mobile (physically active) or immobile (sedentary) running wheel and exposed to either stress (inescapable tail shock) or no stress (home cage control). Voluntary wheel running began 4 wk before stressor exposure. Immediately before stress, all rats were administered an intraperitoneal injection of keyhole limpet hemocyanin (KLH; 200 μg), and anti-KLH Ig was measured weekly for 4 wk using ELISA. Prior physical activity reduced the stress-induced behavioral depression and prevented the stress-induced suppression of anti-KLH IgM and IgG2a antibodies. Anti-KLH IgG1 was stress insensitive. These data suggest that physical activity can buffer the negative impact of stress on behavior and acquired immune function.

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Adsorption of 17α-Ethinyl Estradiol and Bisphenol A to Graphene-Based Materials: Effects of Configuration of Adsorbates and the Presence of Cationic Surfactant

Adsorption Science & Technology ◽

10.1155/2021/9970268 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Fang Wang ◽

Wei Sha ◽

Xin Wang ◽

Yuntao Shang ◽

Lei Hou ◽

...

Keyword(s):

Bisphenol A ◽

Ethinyl Estradiol ◽

Endocrine Disrupting Chemicals ◽

Graphene Oxides ◽

Acceptor Interaction ◽

Reduced Graphene ◽

Deformable Structure ◽

Pore Blockage ◽

Donor Acceptor ◽

Blockage Effect

Endocrine-disrupting chemicals (EDCs) have attracted much attention in recent years. Graphene-based materials (GMs) have been deemed as excellent adsorbents for the removal of EDCs. The objective of the present study was to understand how the cationic surfactants (CTAB; cetyltrimethylammonium nitrate) affect the adsorption of EDCs (17α-ethinyl estradiol (EE2) and bisphenol A (BPA)) on graphene oxide (GO), reduced graphene oxides (RGOs), and the few-layered commercial graphene (CG). It was observed that the presence of CTAB showed different effects on the adsorption of EDCs to different GMs. The adsorption of EDCs on GO was enhanced because of the enhanced hydrophobicity of GMs after the adsorption of CTAB and the newly formed hemimicelles by the adsorbed CTAB, which could serve as the partition phase for EDCs. Moreover, the electron donor-acceptor interaction and cation bridging effect of the –NH4+ group of the adsorbed CTAB between EDCs and GMs could also enhance the adsorption of EDCs to GMs. With the increase of the extent of GM reduction, the adsorption enhancement by the presence of CTAB weakened. This could be attributed to the competition and pore blockage effect caused by the adsorbed CTAB. It is worth noting that the enhancement of CTAB on the adsorption of BPA to GMs was more profound than that of EE2. This is likely because the pore blockage effect plays a less important role in the adsorption of BPA due to its smaller molecular diameter and deformable structure.

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Examination of nucleus accumbens mechanisms underlying the motivation for physical activity

10.32469/10355/63870 ◽

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.

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