Possible mechanisms of metabolic dysfunction in ovariectomized rats : impact of intrinsic aerobic fitness

2015 ◽  
Author(s):  
◽  
Young-Min Park

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Ovariectomized (OVX) rodents are used as a model of human menopause as frequently both experience weight gain, decreased insulin sensitivity and decreased physical activity, which may manifest into metabolic syndrome. Intrinsic aerobic capacity may influence OVX-induced metabolic dysfunction. Female rats selectively bred for high (HCR) and low (LCR) aerobic capacity were used to elucidate the underlying mechanisms by which intrinsic aerobic fitness impacts OVX-associated metabolic dysfunction. We demonstrated that HCR were not fully protected against an OVX-induced decline in insulin sensitivity partially due to a [about]30% attenuation of insulin-stimulated skeletal muscle glucose uptake. HCROVX were protective against HFD-associated insulin resistance through a unique mechanism of behavioral change (i.e. compensatory increase in spontaneous physical activity), while LCROVX exacerbated insulin resistance following HFD. HCR were not protected from OVX-induced reduction in voluntary wheel running; yet HCRhad greater DA activation, compared to LCR, which was associated with their enhanced running distance. Collectively, these data suggest that high aerobic fitness may play a critical role in attenuating metabolic dysfunction associated with OVX and external stress due to their intrinsically enhanced insulin sensitivity. However, high aerobic fitness is not fully protective to OVX-induced impairments in metabolic function and physical activity levels, indicative of a strong physiological effect of ovarian hormone loss.

2015 ◽  
Vol 308 (6) ◽  
pp. R530-R542 ◽  
Author(s):  
Victoria J. Vieira-Potter ◽  
Jaume Padilla ◽  
Young-Min Park ◽  
Rebecca J. Welly ◽  
Rebecca J. Scroggins ◽  
...  

Ovariectomized rodents model human menopause in that they rapidly gain weight, reduce spontaneous physical activity (SPA), and develop metabolic dysfunction, including insulin resistance. How contrasting aerobic fitness levels impacts ovariectomy (OVX)-associated metabolic dysfunction is not known. Female rats selectively bred for high and low intrinsic aerobic fitness [high-capacity runners (HCR) and low-capacity runners (LCR), respectively] were maintained under sedentary conditions for 39 wk. Midway through the observation period, OVX or sham (SHM) operations were performed providing HCR-SHM, HCR-OVX, LCR-SHM, and LCR-OVX groups. Glucose tolerance, energy expenditure, and SPA were measured before and 4 wk after surgery, while body composition via dual-energy X-ray absorptiometry and adipose tissue distribution, brown adipose tissue (BAT), and skeletal muscle phenotype, hepatic lipid content, insulin resistance via homeostatic assessment model of insulin resistance and AdipoIR, and blood lipids were assessed at death. Remarkably, HCR were protected from OVX-associated increases in adiposity and insulin resistance, observed only in LCR. HCR rats were ∼30% smaller, had ∼70% greater spontaneous physical activity (SPA), consumed ∼10% more relative energy, had greater skeletal muscle proliferator-activated receptor coactivator 1-alpha, and ∼40% more BAT. OVX did not increase energy intake and reduced SPA to the same extent in both HCR and LCR. LCR were particularly affected by an OVX-associated reduction in resting energy expenditure and experienced a reduction in relative BAT; resting energy expenditure correlated positively with BAT across all animals ( r = 0.6; P < 0.001). In conclusion, despite reduced SPA following OVX, high intrinsic aerobic fitness protects against OVX-associated increases in adiposity and insulin resistance. The mechanism may involve preservation of resting energy expenditure.


2021 ◽  
Vol 19 (1) ◽  
pp. 21-28
Author(s):  
P. Tayfur ◽  
K. Gökçe Tezel ◽  
Ö. Barutçu ◽  
S. Yılmaz ◽  
E. Ö. Özgür ◽  
...  

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.


2003 ◽  
Vol 60 (6) ◽  
pp. 683-690
Author(s):  
Milica Cizmic ◽  
Mirjana Zivotic-Vanovic ◽  
Slobodan Zivanic ◽  
Radosav Dragojevic

It is well known that under the influence of regular, individually measured aerobic physical activity, it is possible to raise the biological efficiency of insulin by several mechanisms: by increasing the number of insulin receptors, their sensitivity and efficiency, as well as by increasing glucose transporters GLUT-4 on the level of cell membrane. The aim of this research was to examine whether decreased insulin resistance could be achieved under the influence of the program of individually measured aerobic physical activity in the 2-week period, in the obese type 2 diabetes patients with the increased aerobic capacity (VO2)max. In 10 type 2 diabetes patients 47.6 ? 4.6 years of age (group E), in the 14-days period, program of aerobic training was applied (10 sessions - 35 min session of walking on treadmill, intensity 60.8 ? 5.7% (VO2)max, frequency 5 times a week ), as well as 1 600 kcal diet. At the same time, other 10 type 2 diabetes patients 45.9 ? 5.5 years of age (group C) were on 1 600 kcal diet. Before and after this period the following was measured in both groups: insulin sensitivity (M/I) by the method of hyperinsulin euglycemic clamp, and (VO2)max by Astrand test on ergocycle. In contrast to the group C, in the second testing of E group subjects a significant increase was obtained in M/I (1.23 ? 0.78 vs. 2.42 ? 0.95 mg/kg/min/mU p<0.001, 96.75%) as well as the increase of (VO2)max (26.34 ? 4.26 vs. 29.16 ? 5.01 ml/kg/min p<0.05, 10.7%). The results had shown that 2-week program of aerobic training had had significant influence on the increased aerobic capacity and insulin sensitivity in the tested patients.


2007 ◽  
Vol 64 (6) ◽  
pp. 391-397 ◽  
Author(s):  
Radivoj Kocic ◽  
Dusica Pavlovic ◽  
Gordana Kocic ◽  
Milica Pesic

Background/Aim. Oxidative stress plays a critical role in the pathogenesis of various diseases. Recent reports indicate that obesity may induce systemic oxidative stress. The aim of the study was to potentiate oxidative stress as a factor which may aggravate peripheral insulin sensitivity and insulinsecretory response in obesity in this way to potentiate development of diabetes. The aim of the study was also to establish whether insulin-secretory response after glucagonstimulated insulin secretion is susceptible to prooxidant/ antioxidant homeostasis status, as well as to determine the extent of these changes. Methods. A mathematical model of glucose/insulin interactions and C-peptide was used to indicate the degree of insulin resistance and to assess their possible relationship with altered antioxidant/prooxidant homeostasis. The study included 24 obese healthy and 16 obese newly diagnozed non-insulin dependent diabetic patients (NIDDM) as well as 20 control healthy subjects, matched in age. Results. Total plasma antioxidative capacity, erythrocyte and plasma reduced glutathione level were significantly decreased in obese diabetic patients, but also in obese healthy subjects, compared to the values in controls. The plasma lipid peroxidation products and protein carbonyl groups were significantly higher in obese diabetics, more than in obese healthy subjects, compared to the control healthy subjects. The increase of erythrocyte lipid peroxidation at basal state was shown to be more pronounced in obese daibetics, but the apparent difference was obtained in both the obese healthy subjects and obese diabetics, compared to the control values, after exposing of erythrocytes to oxidative stress induced by H2O2. Positive correlation was found between the malondialdehyde (MDA) level and index of insulin sensitivity (FIRI). Conclusion. Increased oxidative stress together with the decreased antioxidative defence seems to contribute to decreased insulin sensitivity and impaired insulin secretory response in obese diabetics, and may be hypothesized to favour the development of diabetes during obesity.


Author(s):  
Kirstin A MacGregor ◽  
Iain J Gallagher ◽  
Colin N Moran

Abstract Context There is evidence demonstrating variation in insulin sensitivity across the menstrual cycle. However, to date, research has yielded inconsistent results. Objective This study investigated variation in insulin sensitivity across the menstrual cycle and associations with BMI, physical activity and cardiorespiratory fitness. Design Data from 1906 premenopausal women in NHANES cycles 1999-2006 were analysed. Main outcome measures Menstrual cycle day was assessed using questionnaire responses recording days since last period. Rhythmic variation of plasma glucose, triglyceride and insulin, homeostatic model of insulin resistance (HOMA-IR) and adipose tissue insulin resistance index (ADIPO-IR) across the menstrual cycle were analysed using cosinor rhythmometry. Participants were assigned low or high categories of BMI, physical activity and cardiorespiratory fitness and category membership included in cosinor models as covariates. Results Rhythmicity was demonstrated by a significant cosine fit for glucose (p= 0.014) but not triglyceride (p= 0.369), insulin (p= 0.470), HOMA-IR (p=0.461) and ADIPO-IR (p= 0.335). When covariates were included, rhythmicity was observed when adjusting for: 1. BMI: glucose (p&lt; 0.001), triglyceride (p&lt; 0.001), insulin (p&lt; 0.001), HOMA-IR (p&lt; 0.001) and ADIPO-IR (p&lt; 0.001); 2. Physical activity: glucose (p&lt; 0.001), triglyceride (p= 0.006) and ADIPO-IR (p= 0.038); 3. Cardiorespiratory fitness: triglyceride (p= 0.041), insulin (p= 0.002), HOMA-IR (p= 0.004) and ADIPO-IR (p= 0.004). Triglyceride amplitude, but not acrophase, was greater in the high physical activity category compared to low (p=0.018). Conclusions Rhythmicity in insulin sensitivity and associated metabolites across the menstrual cycle are modified by BMI, physical activity and cardiorespiratory fitness.


2014 ◽  
Author(s):  
◽  
Leryn J. Boyle

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Individuals with type 2 diabetes (T2D) have blunted femoral artery insulin mediated blood flow which is critical for the delivery and uptake of glucose into skeletal muscle. However, it is unclear in humans the precise mechanisms by which insulin resistance impairs insulin stimulated blood flow. Further, chronic physical inactivity is a powerful stimulus for reduced insulin sensitivity and vascular dysfunction; however, the effects of short term, modest reductions in physical activity are limited. Thus, we examined 1) if inactivity for 5 days would impair endothelial function in healthy individuals (study one) 2) if reducing whole body insulin sensitivity, via 5 days of inactivity, would impair the blood flow response to insulin stimulation in parallel with glycemic control (study two) and 3) phosphorylation of endothelial nitric oxide (eNOS) and endothelin-1 (ET-1) production to insulin stimulation would be decreased and increased, respectively, in insulin resistant individuals (study three). We demonstrated significant reductions in endothelial function with only 5 days of reduced daily steps while blood flow to glucose ingestion was unaltered. Further, in obese humans with type 2 diabetes it does not appear that that the reduction in blood flow to 1 hr of insulin stimulation is due to altered peNOS or ET-1. Collectively, these data suggest that reduced daily physical activity and chronic insulin resistance mediate negative impacts on vascular function and insulin stimulated blood flow and signaling.


2020 ◽  
Vol 21 (4) ◽  
pp. 1514 ◽  
Author(s):  
Paul T. Reidy ◽  
Ziad S. Mahmassani ◽  
Alec I. McKenzie ◽  
Jonathan J. Petrocelli ◽  
Scott A. Summers ◽  
...  

Intramuscular lipid accumulation has been associated with insulin resistance (IR), aging, diabetes, dyslipidemia, and obesity. A substantial body of evidence has implicated ceramides, a sphingolipid intermediate, as potent antagonists of insulin action that drive insulin resistance. Indeed, genetic mouse studies that lower ceramides are potently insulin sensitizing. Surprisingly less is known about how physical activity (skeletal muscle contraction) regulates ceramides, especially in light that muscle contraction regulates insulin sensitivity. The purpose of this review is to critically evaluate studies (rodent and human) concerning the relationship between skeletal muscle ceramides and IR in response to increased physical activity. Our review of the literature indicates that chronic exercise reduces ceramide levels in individuals with obesity, diabetes, or hyperlipidemia. However, metabolically healthy individuals engaged in increased physical activity can improve insulin sensitivity independent of changes in skeletal muscle ceramide content. Herein we discuss these studies and provide context regarding the technical limitations (e.g., difficulty assessing the myriad ceramide species, the challenge of obtaining information on subcellular compartmentalization, and the paucity of flux measurements) and a lack of mechanistic studies that prevent a more sophisticated assessment of the ceramide pathway during increased contractile activity that lead to divergences in skeletal muscle insulin sensitivity.


2010 ◽  
Vol 35 (2) ◽  
pp. 151-162 ◽  
Author(s):  
Scott P. Naples ◽  
Sarah J. Borengasser ◽  
R. Scott. Rector ◽  
Grace M. Uptergrove ◽  
E. Matthew Morris ◽  
...  

Rats selected artificially to be low-capacity runners (LCR) possess a metabolic syndrome phenotype that is worsened by a high-fat diet (HFD), whereas rats selected to be high-capacity runners (HCR) are protected against HFD-induced obesity and insulin resistance. This study examined whether protection against, or susceptibility to, HFD-induced insulin resistance in the HCR–LCR strains is associated with contrasting metabolic adaptations in skeletal muscle. HCR and LCR rats (generation 20; n = 5–6; maximum running distance ∼1800 m vs. ∼350 m, respectively (p < 0.0001)) were divided into HFD (71.6% energy from fat) or normal chow (NC) (16.7% energy from fat) groups for 7 weeks (from 24 to 31 weeks of age). Skeletal muscle (red gastrocnemius) mitochondrial-fatty acid oxidation (FAO), mitochondrial-enzyme activity, mitochondrial-morphology, peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), and peroxisome proliferator-activated receptor δ (PPARδ) expression and insulin sensitivity (intraperitoneal glucose tolerance tests) were measured. The HFD caused increased adiposity and reduced insulin sensitivity only in the LCR and not the HCR strain. Isolated mitochondria from the HCR skeletal muscle displayed a 2-fold-higher rate of FAO on NC, but both groups increased FAO following HFD. PGC-1α mRNA expression and superoxide dismutase activity were significantly reduced with the HFD in the LCR rats, but not in the HCR rats. PPARδ expression did not differ between strains or dietary conditions. These results do not provide a clear connection between protection of insulin sensitivity and HFD-induced adaptive changes in mitochondrial function or transcriptional responses but do not dismiss the possibility that elevated mitochondrial FAO in the HCR may play a protective role.


2006 ◽  
Vol 163 (10) ◽  
pp. 921-928 ◽  
Author(s):  
Capri Gabrielle Foy ◽  
Kristie Long Foley ◽  
Ralph B. D'Agostino ◽  
David C. Goff ◽  
Elizabeth Mayer-Davis ◽  
...  

2013 ◽  
Vol 5 (1) ◽  
pp. 93-98
Author(s):  
Annie McGee ◽  
Skip M. Williams ◽  
Margaret M. Coleman ◽  
Amy Hurd ◽  
Kelly R. Laurson

Summary Study aim: The purpose of this study was to examine if step-counts during PE and self-reported PA of elementary grade students varied based on the aerobic capacity. Material and methods: Ninety elementary physical education students, enrolled in the 4th and 5th grade, from one elementary school in the Midwestern USA participated. Each participant completed the Physical Activity Questionnaire for Children (PAQ-C), wore a pedometer in PE to measure steps taken, and completed the PACER aerobic fitness test. A multiple regression analysis was conducted to determine the relationship between steps taken by students and PAQ-C score in predicting aerobic capacity as measured through the PACER test. Results: Average steps significantly predicted PACER laps (β = 0.48, p < 0.01), as did the PAQ-C (β = 0.28, p < 0.001). For males, average steps significantly predicted PACER laps (β = 0.48 p < 0.01), while the PAQ-C and the PACER beta coefficients were not statistically significant (β = 0.14, p = 0.30). Results for females indicated average steps significantly predicted PACER laps (β = 0.38, p < 0.01), as did the PAQ-C (β = 0.46, p < 0.001). Conclusion: Results from this study indicate that student steps taken during PE and self-report PA has an association with students’ completed PACER laps.


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