scholarly journals Dietary Supplementation With Montmorency Tart Cherries and Exercise Improves Lean Mass in Older C57BL/6 Mice

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 45-45
Author(s):  
Kara Robinson ◽  
Bethany Hatter ◽  
Karley Washburn ◽  
James Bothwell ◽  
Kendall Anderson ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
Muscle Mass ◽  
Mitochondrial Biogenesis ◽  
Lean Mass ◽  
Treadmill Running ◽  
Peroxisome Proliferator ◽  
Research Committee ◽  
Peroxisome Proliferator Activated Receptor ◽  
Young Mice

Abstract Objectives Sarcopenia, the progressive loss of muscle mass and strength, accelerates with age. Current recommendations to prevent sarcopenia focus on exercise and protein intake. Tart cherry (TC) has shown beneficial effects on muscle recovery following exercise. In this study, we investigated the effects of TC alone and in combination with exercise on lean mass, mitochondrial biogenesis, and oxidative stress in young compared to older mice. Methods In two cohorts (6 & 52 wk-old), female C57BL/6 mice were randomly assigned to 4 groups in a 2 × 2 factorial design with diet (AIN-93 control or TC supplemented at 10% w/w) and exercise as factors. Exercise consisted of treadmill running for 30 min, 5 d/wk, at 12 m/min and a 5° incline. Food intake was recorded daily and body weights weekly. After 8 wks, body composition was assessed using dual-energy x-ray absorptiometry. The gastrocnemius muscle was collected for protein analysis. Western blotting techniques were used to probe for superoxide dismutase 2 (SOD2) and peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC1a), indicators of oxidative stress and mitochondrial biogenesis. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was used as loading control. Data were analyzed using 2-way ANOVA with α = 0.05. Results In young mice, TC had no effect on body weight and % lean mass, but led to decreased (P < 0.05) % fat mass compared to controls. Exercise decreased (P < 0.05) body weight and % fat, and tended to increase (P = 0.069) % lean mass. In contrast, TC and exercise independently decreased body weight and % fat, and increased % lean mass in older mice compared to controls. The combination of TC and exercise tended to have a synergistic effect on % lean mass (P = 0.056). Preliminary results show that TC significantly up-regulated SOD2 protein expression in young mice, but no effect was observed with exercise or combined treatments. PGC1α expression tended to be suppressed (P = 0.064) in young animals fed TC. To date, we have been unable to detect changes in SOD2 and PGC1α in older mice. Conclusions TC had a protective effect on lean tissue in older mice, preliminary analyses revealed no alterations in oxidative stress or mitochondrial biogenesis. Further investigation is warranted to understand the benefits of TC on lean muscle mass in older mice. Funding Sources Cherry Research Committee of the Cherry Marketing Institute

Combination of Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) Agonist and PPAR Gamma Co-Activator 1α (PGC-1α) Activator Ameliorates Cognitive Deficits, Oxidative Stress, and Inflammation in Rodent Model of Parkinson's Disease

2021 ◽  
Vol 19 ◽  
Author(s):  
Nihar Ranjan Das ◽  
Bhupesh Vaidya ◽  
Pragyanshu Khare ◽  
Mahendra Bishnoi ◽  
Shyam Sunder Sharma
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Lipoic Acid ◽  
Mitochondrial Biogenesis ◽  
Cognitive Deficits ◽  
Ppar Gamma ◽  
Peroxisome Proliferator ◽  
Alpha Lipoic Acid ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pparγ Agonist

Background: PPAR gamma co-activator 1α (PGC-1α) is known as the master regulator of mitochondrial biogenesis. It is also a co-activator of peroxisome proliferator-activated receptor-gamma (PPARγ) and plays a role in preventing mitochondrial dysfunction in several neurodegenerative disorders, including Parkinson’s disease (PD). Depletion in the levels of these proteins has been linked to oxidative stress, inflammation, and DNA damage, all of which are known to contribute to the pathogenesis of PD. Objective: In the present study, combination therapy of PPARγ agonist (GW1929) and PGC-1α activator (alpha-lipoic acid) was employed to ameliorate cognitive deficits, oxidative stress, and inflammation associated with the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD. Results: Our study showed that MPTP-induced PD rats exhibited an increase in oxidative stress and inflammation, leading to cognitive deficits. Furthermore, MPTP-induced PD rats also exhibited reduced mitochondrial biogenesis in comparison to control and sham animals. Intraperitoneal administration of GW 1929 and alpha-lipoic acid in doses lower than those earlier reported individually in literature led to an improvement in the cognitive deficits in comparison to MPTP-induced PD rats. These improvements were accompanied by a reduction in the levels of oxidative stress and inflammation. In addition, an increase in mitochondrial biogenesis was also observed after the combination of these pharmacological agents. Conclusion: Our results provide a rationale for the development of agents targeting PPARγ and PGC-1α as potent therapeutics for the treatment of neurological diseases like PD.

scholarly journals Exercise training increases mitochondrial biogenesis in the brain

2011 ◽  
Vol 111 (4) ◽  
pp. 1066-1071 ◽  
Author(s):  
Jennifer L. Steiner ◽  
E. Angela Murphy ◽  
Jamie L. McClellan ◽  
Martin D. Carmichael ◽  
J. Mark Davis
Keyword(s):  
Exercise Training ◽  
Mitochondrial Biogenesis ◽  
Citrate Synthase ◽  
Brain Mitochondria ◽  
Brain Regions ◽  
Treadmill Running ◽  
Endurance Capacity ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Age Related

Increased muscle mitochondria are largely responsible for the increased resistance to fatigue and health benefits ascribed to exercise training. However, very little attention has been given to the likely benefits of increased brain mitochondria in this regard. We examined the effects of exercise training on markers of both brain and muscle mitochondrial biogenesis in relation to endurance capacity assessed by a treadmill run to fatigue (RTF) in mice. Male ICR mice were assigned to exercise (EX) or sedentary (SED) conditions ( n = 16–19/group). EX mice performed 8 wk of treadmill running for 1 h/day, 6 days/wk at 25 m/min and a 5% incline. Twenty-four hours after the last training bout a subgroup of mice ( n = 9–11/group) were euthanized, and brain (brain stem, cerebellum, cortex, frontal lobe, hippocampus, hypothalamus, and midbrain) and muscle (soleus) tissues were isolated for analysis of mRNA expression of peroxisome proliferator-activated receptor-gamma coactivator-1-alpha (PGC-1α), Silent Information Regulator T1 (SIRT1), citrate synthase (CS), and mitochondrial DNA (mtDNA) using RT-PCR. A different subgroup of EX and SED mice ( n = 7–8/group) performed a treadmill RTF test. Exercise training increased PGC-1α, SIRT1, and CS mRNA and mtDNA in most brain regions in addition to the soleus ( P < 0.05). Mean treadmill RTF increased from 74.0 ± 9.6 min to 126.5 ± 16.1 min following training ( P < 0.05). These findings suggest that exercise training increases brain mitochondrial biogenesis, which may have important implications, not only with regard to fatigue, but also with respect to various central nervous system diseases and age-related dementia that are often characterized by mitochondrial dysfunction.

scholarly journals Rhein Relieves Oxidative Stress in an Aβ1-42 Oligomer-Burdened Neuron Model by Activating the SIRT1/PGC-1α-Regulated Mitochondrial Biogenesis

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhihui Yin ◽  
Xinyue Geng ◽  
Zhengyi Zhang ◽  
Ying Wang ◽  
Xiaoyan Gao
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Biogenesis ◽  
Antioxidant Defense System ◽  
Sirtuin 1 ◽  
Early Event ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mitochondrial Oxidative Stress ◽  
Nuclear Respiratory Factor ◽  
Nuclear Respiratory Factor 1

Neuronal mitochondrial oxidative stress induced by β-amyloid (Aβ) is an early event of Alzheimer’s disease (AD). Emerging evidence has shown that antioxidant therapy represents a promising therapeutic strategy for the treatment of AD. In this study, we investigated the antioxidant activity of rhein against Aβ1-42 oligomer-induced mitochondrial oxidative stress in primary neurons and proposed a potential antioxidant pathway involved. The results suggested that rhein significantly reduced reactive oxygen species (ROS) level, reversed the depletion of mitochondrial membrane potential, and protected neurons from oxidative stress-associated apoptosis. Moreover, further study indicated that rhein activated mitochondrial biogenesis accompanied by increased cytochrome C oxidase (CytOx) and superoxide dismutase (SOD) activities. CytOx on the respiratory chain inhibited the production of ROS from electron leakage and SOD helped to eliminate excess ROS. Finally, western blot analysis confirmed that rhein remarkedly increased the protein expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) together with its upstream deacetylase sirtuin 1 (SIRT1), and activated downstream transcription factor nuclear respiratory factor 1, promoting mitochondrial biogenesis. In conclusion, our results demonstrate that rhein activates mitochondrial biogenesis regulated by the SIRT1/PGC-1α pathway as an antioxidant defense system against Aβ1-42 oligomer-induced oxidative stress. These findings broaden our knowledge of improving mitochondrial biogenesis as an approach for relieving neuronal oxidative stress in AD.

scholarly journals Heat-Killed Bifidobacterium breve B-3 Enhances Muscle Functions: Possible Involvement of Increases in Muscle Mass and Mitochondrial Biogenesis

Nutrients ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 219
Author(s):  
Kazuya Toda ◽  
Yuki Yamauchi ◽  
Azusa Tanaka ◽  
Tetsuya Kuhara ◽  
Toshitaka Odamaki ◽  
...  
Keyword(s):  
Muscle Mass ◽  
Mitochondrial Biogenesis ◽  
Muscle Metabolism ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Bifidobacterium Breve ◽  
Metabolic Functions ◽  
Group B ◽  
Amp Activated Protein Kinase

A previous clinical study on pre-obesity subjects revealed that Bifidobacterium breve B-3 shows anti-obesity effects and possibly increases muscle mass. Here, we investigated the effects of B-3 on muscle function, such as muscle strength and metabolism, and some signaling pathways in skeletal muscle. Male rodents were orally administered live B-3 (B-3L) or heat-killed B-3 (B-3HK) for 4 weeks. We found that administration of B-3 to rats tended to increase muscle mass and affect muscle metabolism, with stronger effects in the B-3HK group than in the B-3L group. B-3HK significantly increased muscle mass and activated Akt in the rat soleus. With regard to muscle metabolism, B-3HK significantly increased phosphorylated AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α and cytochrome c oxidase (CCO) gene expression in the rat soleus, suggesting an effect on the AMPK-PGC1α-mitochondrial biogenesis pathway. Furthermore, B-3HK promoted oxidative muscle fiber composition in the gastrocnemius. We also observed a significantly higher level of murine grip strength in the B-3HK group than in the control group. These findings suggest the potential of heat-killed B-3 in promoting muscle hypertrophy and modifying metabolic functions, possibly through the Akt and AMPK pathways, respectively.

Muscle immobilization and remobilization downregulates PGC-1α signaling and the mitochondrial biogenesis pathway

2013 ◽  
Vol 115 (11) ◽  
pp. 1618-1625 ◽  
Author(s):  
Chounghun Kang ◽  
Li Li Ji
Keyword(s):  
Oxidative Stress ◽  
Cytochrome C ◽  
Muscle Atrophy ◽  
Mitochondrial Biogenesis ◽  
Skeletal Muscle Atrophy ◽  
Control Group ◽  
Ros Generation ◽  
Peroxisome Proliferator ◽  
Protein Loss ◽  
Peroxisome Proliferator Activated Receptor

Prolonged immobilization (IM) results in skeletal muscle atrophy accompanied by increased reactive oxygen species (ROS) generation, inflammation, and protein degradation. However, the biological consequence of remobilizing such muscle has been studied only sparsely. In this study, we examined the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α)-controlled mitochondrial biogenesis pathway and inflammatory response in mice subjected to 2 wk of hindlimb IM followed by 5 days of remobilization (RM). We hypothesized that ROS generation and activation of redox-sensitive signaling pathways play important roles in the etiology of muscle injury. FVB/N mice (age 2 mo) were randomly assigned to either 14 days of IM by casting one of the hindlimbs ( n = 7), IM followed by 5 days of RM with casting removed ( n = 7), or to a control group (Con; n = 7). Muscle to body weight ratios of three major leg muscles were significantly decreased as a result of IM. Two ubiquitin-proteasome pathway enzymes, muscle atrophy F-box (MAFb or atrogin-1) and muscle ring finger-1 (MuRF-1), were upregulated with IM and maintained at high levels during RM. Protein contents of PGC-1α and nuclear respiratory factors 1 and 2 in tibialis anterior (TA) muscle were reduced by 50% ( P < 0.01) in IM vs. Con, with no recovery observed during RM. IM suppressed mitochondrial transcription factor A and cytochrome- c content by 57% and 63% ( P < 0.01), respectively, and cytochrome- c oxidase activity by 58% ( P < 0.05). Furthermore, mitochondrial DNA content was reduced by 71% ( P < 0.01) with IM. None of these changes were reversed after RM. With RM, TA muscle showed a 2.3-fold ( P < 0.05) higher H2O2 content and a 4-fold ( P < 0.01) higher 8-isoprostane content compared with Con, indicating oxidative stress. Tumor necrosis factor-α and interleukin-6 levels in TA muscle were 4- and 3-fold higher ( P < 0.05), respectively, in IM and RM vs. CON. The nuclear factor-κB (NF-κB) pathway activation was observed only after RM, but not after IM alone. These data indicate an increase in ROS generation during the initial phase of muscle RM that could activate the NF-κB pathway, and elicit inflammation and oxidative stress. These events may hinder muscle recovery from IM-induced mitochondrial deterioration and protein loss.

Abstract 292: Brain Derived Neurotrophic Factor Induced Upregulation Of Peroxisome Proliferator-activated Receptor Gamma Coactivator 1-alpha Signaling Prevents Hearts From Heart Failure Progression Against Pressure Overload

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Ning Feng ◽  
Guangshuo Zhu ◽  
vidhya Sivakumaran ◽  
Manling Zhang ◽  
Djahida Bedja ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Cardiac Function ◽  
Mitochondrial Biogenesis ◽  
Neurotrophic Factor ◽  
Pressure Overload ◽  
Brain Derived Neurotrophic Factor ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Bdnf Signaling

Background: The heart is under the influence of neurotrophins (NTs) secreted from peripheral sympathetic nerves, including brain derived neurotrophic factor (BDNF). BDNF is indispensible for cardiac development and vascular wall integrity. Yet, whether BDNF signaling plays a role in governing cardiac function in response to stress is unclear. Hypothesis: BDNF signaling contributes to maintain proper cardiac structure/function in pressure overloaded mice. Results: BDNF expression is markedly down-regulated in hearts subjected to transverse aortic constriction (TAC). Cardiac specific over-expression of BDNF (BDNF-TG) or administration of a BDNF-mimetic agonist (LM22A-4) preserved cardiac function against pressure overload. In contrast, cardiac-selective deletion of the BDNF receptor, Tropomyosin related kinase receptor B (TrkB), further exacerbated heart failure. In neurons, BDNF up-regulates Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) that regulates energy metabolism and mitochondrial function/biogenesis. Oxidative stress is a major negative modulator of PGC-1a expression/activity. Exposing neonatal rat ventricular myocytes (NRVMs) to hydrogen peroxide downregulated PGC-1α, and BDNF restored it to normal levels, with a concomitant up-regulation of downstream genes involved in both mitochondrial biogenesis and oxidative stress, resulting in attenuated ROS production and increased mitochondrial biogenesis. Consistent with the cultured myocyte findings, PGC-1α and downstream genes were up-regulated in BDNF-TG mice subjected to TAC, associated with attenuated oxidative stress and improved mitochondrial biogenesis; whereas TrkB-/- mice subjected to TAC displayed further decreased PGC-1α expression with worsened oxidative stress and impaired mitochondrial biogenesis. Conclusion: Our data show that BDNF confers protection against pressure overload via enhanced PGC-1α signaling that in turn prevents oxidative stress and improves mitochondrial biogenesis. Our data suggest BDNF/trkB is a promising new therapeutic avenue to prevent or retard heart failure.

Natural Aldose Reductase Inhibitor: A Potential Therapeutic Agent for Non-alcoholic Fatty Liver Disease

2020 ◽  
Vol 21 (6) ◽  
pp. 599-609 ◽  
Author(s):  
Longxin Qiu ◽  
Chang Guo
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Fatty Liver ◽  
Aldose Reductase ◽  
Fatty Liver Disease ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver

Aldose reductase (AR) has been reported to be involved in the development of nonalcoholic fatty liver disease (NAFLD). Hepatic AR is induced under hyperglycemia condition and converts excess glucose to lipogenic fructose, which contributes in part to the accumulation of fat in the liver cells of diabetes rodents. In addition, the hyperglycemia-induced AR or nutrition-induced AR causes suppression of the transcriptional activity of peroxisome proliferator-activated receptor (PPAR) α and reduced lipolysis in the liver, which also contribute to the development of NAFLD. Moreover, AR induction in non-alcoholic steatohepatitis (NASH) may aggravate oxidative stress and the expression of inflammatory cytokines in the liver. Here, we summarize the knowledge on AR inhibitors of plant origin and review the effect of some plant-derived AR inhibitors on NAFLD/NASH in rodents. Natural AR inhibitors may improve NAFLD at least in part through attenuating oxidative stress and inflammatory cytokine expression. Some of the natural AR inhibitors have been reported to attenuate hepatic steatosis through the regulation of PPARα-mediated fatty acid oxidation. In this review, we propose that the natural AR inhibitors are potential therapeutic agents for NAFLD.

scholarly journals PPAR-gamma induced AKT3 expression increases levels of mitochondrial biogenesis driving prostate cancer

Oncogene ◽  
2021 ◽  
Vol 40 (13) ◽  
pp. 2355-2366
Author(s):  
Laura C. A. Galbraith ◽  
Ernest Mui ◽  
Colin Nixon ◽  
Ann Hedley ◽  
David Strachan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Mitochondrial Biogenesis ◽  
Nuclear Export ◽  
Epithelial To Mesenchymal Transition ◽  
Ppar Gamma ◽  
Peroxisome Proliferator ◽  
Serine Threonine Kinase ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mesenchymal Transition ◽  
And Function

AbstractPeroxisome Proliferator-Activated Receptor Gamma (PPARG) is one of the three members of the PPAR family of transcription factors. Besides its roles in adipocyte differentiation and lipid metabolism, we recently demonstrated an association between PPARG and metastasis in prostate cancer. In this study a functional effect of PPARG on AKT serine/threonine kinase 3 (AKT3), which ultimately results in a more aggressive disease phenotype was identified. AKT3 has previously been shown to regulate PPARG co-activator 1 alpha (PGC1α) localisation and function through its action on chromosome maintenance region 1 (CRM1). AKT3 promotes PGC1α localisation to the nucleus through its inhibitory effects on CRM1, a known nuclear export protein. Collectively our results demonstrate how PPARG over-expression drives an increase in AKT3 levels, which in turn has the downstream effect of increasing PGC1α localisation within the nucleus, driving mitochondrial biogenesis. Furthermore, this increase in mitochondrial mass provides higher energetic output in the form of elevated ATP levels which may fuel the progression of the tumour cell through epithelial to mesenchymal transition (EMT) and ultimately metastasis.

The Protective Mechanism of SIRT1 in the Regulation of Mitochondrial Biogenesis and Mitochondrial Autophagy in Alzheimer’s Disease

2021 ◽  
pp. 1-9
Author(s):  
Fan Ye ◽  
Anshi Wu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Biogenesis ◽  
Stress Responses ◽  
Histone Deacetylases ◽  
Neuronal Morphology ◽  
Protective Mechanism ◽  
Peroxisome Proliferator ◽  
Class Iii ◽  
Peroxisome Proliferator Activated Receptor

Silent information-regulated transcription factor 1 (SIRT1) is the most prominent and widely studied member of the sirtuins (a family of mammalian class III histone deacetylases). It is a nuclear protein, and the deacetylation of the peroxisome proliferator-activated receptor coactivator-1 has been extensively implicated in metabolic control and mitochondrial biogenesis and is the basis for studies into its involvement in caloric restriction and its effects on lifespan. The present study discusses the potentially protective mechanism of SIRT1 in the regulation of the mitochondrial biogenesis and autophagy involved in the modulation of Alzheimer’s disease, which may be correlated with the role of SIRT1 in affecting neuronal morphology, learning, and memory during development; regulating metabolism; counteracting stress responses; and maintaining genomic stability. Drugs that activate SIRT1 may offer a promising approach to treating Alzheimer’s disease

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