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

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.

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High expressions of the cytoglobin and PGC-1α genes during the tissue regeneration of house gecko (Hemidactylus platyurus) tails

10.21203/rs.2.12354/v2 ◽

2020 ◽

Author(s):

Titta Novianti ◽

Vetnizah Juniantito ◽

Ahmad Aulia Jusuf ◽

Evy Ayu Arida ◽

Mohamad Sadikin ◽

...

Keyword(s):

Wound Healing ◽

Tissue Regeneration ◽

Mitochondrial Biogenesis ◽

Energy Production ◽

Energy Levels ◽

Regeneration Process ◽

Control Group ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Healing Phase

Abstract Background The tissue regeneration process requires high oxygen and energy levels. Cytoglobin (Cygb) is a member of the globin family, which has the ability to bind oxygen, plays a role in dealing with oxidative stress, and carries oxygen into the mitochondria. Energy production for tissue regeneration is associated with mitochondria—especially mitochondrial biogenesis. The peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha protein helps to regulate mitochondrial biogenesis. House geckos ( Hemidactylus platyurus ) are reptiles that have the ability to regenerate the tissue in their tails. House geckos were selected as the animal models for this study in order to analyze the association of Cygb with oxygen supply and the association of PGC-1α with energy production for tissue regeneration. Results The growth of house gecko tails showed a slow growth at the wound healing phase, then followed by a fast growth after wound healing phase of the regeneration process. While Cygb mRNA expression reached its peak at the wound healing phase and slowly decreased until the end of the observation. PGC-1α mRNA was expressed and reached its peak earlier than Cygb. Conclusions The expressions of both the Cygb and PGC-1α genes were relatively high compared to the control group. We therefore suggest that Cygb and PGC-1α play an important role during the tissue regeneration process. Keywords: cytoglobin, PGC-1α, mitochondrial biogenesis, house gecko, tissue regeneration

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

Journal of Applied Physiology ◽

10.1152/japplphysiol.01354.2012 ◽

2013 ◽

Vol 115 (11) ◽

pp. 1618-1625 ◽

Cited By ~ 40

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.

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Regulation of mitochondrial biogenesis

Essays in Biochemistry ◽

10.1042/bse0470069 ◽

2010 ◽

Vol 47 ◽

pp. 69-84 ◽

Cited By ~ 356

Author(s):

François R. Jornayvaz ◽

Gerald I. Shulman

Keyword(s):

Mitochondrial Dysfunction ◽

Mitochondrial Biogenesis ◽

Molecular Mechanisms ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Nuclear Respiratory Factor ◽

Mitochondrial Transcription Factor ◽

Nuclear Respiratory Factor 1 ◽

And Function ◽

Amp Activated Protein Kinase

Although it is well established that physical activity increases mitochondrial content in muscle, the molecular mechanisms underlying this process have only recently been elucidated. Mitochondrial dysfunction is an important component of different diseases associated with aging, such as Type 2 diabetes and Alzheimer’s disease. PGC-1α (peroxisome-proliferator-activated receptor γ co-activator-1α) is a co-transcriptional regulation factor that induces mitochondrial biogenesis by activating different transcription factors, including nuclear respiratory factor 1 and nuclear respiratory factor 2, which activate mitochondrial transcription factor A. The latter drives transcription and replication of mitochondrial DNA. PGC-1α itself is regulated by several different key factors involved in mitochondrial biogenesis, which will be reviewed in this chapter. Of those, AMPK (AMP-activated protein kinase) is of major importance. AMPK acts as an energy sensor of the cell and works as a key regulator of mitochondrial biogenesis. AMPK activity has been shown to decrease with age, which may contribute to decreased mitochondrial biogenesis and function with aging. Given the potentially important role of mitochondrial dysfunction in the pathogenesis of numerous diseases and in the process of aging, understanding the molecular mechanisms regulating mitochondrial biogenesis and function may provide potentially important novel therapeutic targets.

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

Current Developments in Nutrition ◽

10.1093/cdn/nzab033_045 ◽

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

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High expressions of the cytoglobin and PGC-1α genes during the tissue regeneration of house gecko (Hemidactylus platyurus) tails

10.21203/rs.2.12354/v3 ◽

2020 ◽

Author(s):

Titta Novianti ◽

Vetnizah Juniantito ◽

Ahmad Aulia Jusuf ◽

Evy Ayu Arida ◽

Mohamad Sadikin ◽

...

Keyword(s):

Wound Healing ◽

Tissue Regeneration ◽

Mitochondrial Biogenesis ◽

Energy Production ◽

Energy Levels ◽

Regeneration Process ◽

Control Group ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Healing Phase

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Hypoxic Exposure Increases Energy Expenditure by Increasing Carbohydrate Oxidation in Mice

BioMed Research International ◽

10.1155/2020/6159407 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Yeram Park ◽

Deunsol Hwang ◽

Hun-Young Park ◽

Jisu Kim ◽

Kiwon Lim

Keyword(s):

Glucose Metabolism ◽

Energy Expenditure ◽

Pyruvate Dehydrogenase ◽

Hypoxic Condition ◽

Open Circuit ◽

Pyruvate Dehydrogenase Kinase ◽

Hypoxic Exposure ◽

Control Group ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor

Aims. Hypoxic exposure improves glucose metabolism. We investigated to validate the hypothesis that carbohydrate (CHO) oxidation could increase in mice exposed to severe hypoxic conditions. Methods. Seven-week-old male ICR mice (n=16) were randomly divided into two groups: the control group (CON) was kept in normoxic condition (fraction of inspired O2=21%) and the hypoxia group (HYP) was exposed to hypoxic condition (fraction of inspired O2=12%, ≈altitude of 4,300 m). The CON group was pair-fed with the HYP group. After 3 weeks of hypoxic exposure, we measured respiratory metabolism (energy expenditure and substrate utilization) at normoxic conditions for 24 hours using an open-circuit calorimetry system. In addition, we investigated changes in carbohydrate mechanism-related protein expression, including hexokinase 2 (HK2), pyruvate dehydrogenase (PDH), pyruvate dehydrogenase kinase 4 (PDK4), and regulator of the genes involved in energy metabolism (peroxisome proliferator-activated receptor gamma coactivator 1-alpha, PGC1α) in soleus muscle. Results. Energy expenditure (EE) and CHO oxidation over 24 hours were higher in the HYP group by approximately 15% and 34% (p<0.001), respectively. Fat oxidation was approximately 29% lower in the HYP group than the CON group (p<0.01). Body weight gains were significantly lower in the HYP group than in the CON group (CON vs. HYP; 1.9±0.9 vs. −0.3±0.9; p<0.001). Hypoxic exposure for 3 weeks significantly reduced body fat by approximately 42% (p<0.001). PDH and PGC1α protein levels were significantly higher in the HYP group (p<0.05). Additionally, HK2 was approximately 21% higher in the HYP group. Conclusions. Hypoxic exposure might significantly enhance CHO oxidation by increasing the expression of PDH and HK2. This investigation can be useful for patients with impaired glucose metabolism, such as those with type 2 diabetes.

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

Oncogene ◽

10.1038/s41388-021-01707-7 ◽

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.

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

Journal of Alzheimer s Disease ◽

10.3233/jad-210132 ◽

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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The Demethoxy Derivatives of Curcumin Exhibit Greater Differentiation Suppression in 3T3-L1 Adipocytes Than Curcumin: A Mechanistic Study of Adipogenesis and Molecular Docking

Biomolecules ◽

10.3390/biom11071025 ◽

2021 ◽

Vol 11 (7) ◽

pp. 1025

Author(s):

Ahmed Alalaiwe ◽

Jia-You Fang ◽

Hsien-Ju Lee ◽

Chun-Hui Chiu ◽

Ching-Yun Hsu

Keyword(s):

Molecular Docking ◽

Fatty Acid Synthase ◽

Structural Similarity ◽

Mechanistic Study ◽

Peroxisome Proliferator ◽

Dependent Manner ◽

Peroxisome Proliferator Activated Receptor ◽

Enhancer Binding Protein ◽

Underlying Mechanisms ◽

Amp Activated Protein Kinase

Curcumin is a known anti-adipogenic agent for alleviating obesity and related disorders. Comprehensive comparisons of the anti-adipogenic activity of curcumin with other curcuminoids is minimal. This study compared adipogenesis inhibition with curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC), and their underlying mechanisms. We differentiated 3T3-L1 cells in the presence of curcuminoids, to determine lipid accumulation and triglyceride (TG) production. The expression of adipogenic transcription factors and lipogenic proteins was analyzed by Western blot. A significant reduction in Oil red O (ORO) staining was observed in the cells treated with curcuminoids at 20 μM. Inhibition was increased in the order of curcumin < DMC < BDMC. A similar trend was observed in the detection of intracellular TG. Curcuminoids suppressed differentiation by downregulating the expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), leading to the downregulation of the lipogenic enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). AMP-activated protein kinase α (AMPKα) phosphorylation was also activated by BDMC. Curcuminoids reduced the release of proinflammatory cytokines and leptin in 3T3-L1 cells in a dose-dependent manner, with BDMC showing the greatest potency. BDMC at 20 μM significantly decreased leptin by 72% compared with differentiated controls. Molecular docking computation indicated that curcuminoids, despite having structural similarity, had different interaction positions to PPARγ, C/EBPα, and ACC. The docking profiles suggested a possible interaction of curcuminoids with C/EBPα and ACC, to directly inhibit their expression.

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Progressive Reduction in Mitochondrial Mass Is Triggered by Alterations in Mitochondrial Biogenesis and Dynamics in Chronic Kidney Disease Induced by 5/6 Nephrectomy

Biology ◽

10.3390/biology10050349 ◽

2021 ◽

Vol 10 (5) ◽

pp. 349

Author(s):

Rodrigo Prieto-Carrasco ◽

Fernando E. García-Arroyo ◽

Omar Emiliano Aparicio-Trejo ◽

Pedro Rojas-Morales ◽

Juan Carlos León-Contreras ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Mitochondrial Biogenesis ◽

Renal Mass ◽

Renal Damage ◽

Peroxisome Proliferator ◽

Progressive Reduction ◽

Ckd Progression ◽

Peroxisome Proliferator Activated Receptor ◽

Mitochondrial Mass ◽

Mitochondrial Impairment

The five-sixth nephrectomy (5/6Nx) model is widely used to study the mechanisms involved in chronic kidney disease (CKD) progression. Mitochondrial impairment is a critical mechanism that favors CKD progression. However, until now, there are no temporal studies of the change in mitochondrial biogenesis and dynamics that allow determining the role of these processes in mitochondrial impairment and renal damage progression in the 5/6Nx model. In this work, we determined the changes in mitochondrial biogenesis and dynamics markers in remnant renal mass from days 2 to 28 after 5/6Nx. Our results show a progressive reduction in mitochondrial biogenesis triggered by reducing two principal regulators of mitochondrial protein expression, the peroxisome proliferator-activated receptor-gamma coactivator 1-alpha and the peroxisome proliferator-activated receptor alpha. Furthermore, the reduction in mitochondrial biogenesis proteins strongly correlates with the increase in renal damage markers. Additionally, we found a slow and gradual change in mitochondrial dynamics from fusion to fission, favoring mitochondrial fragmentation at later stages after 5/6Nx. Together, our results suggest that 5/6Nx induces the progressive reduction in mitochondrial mass over time via the decrease in mitochondrial biogenesis factors and a slow shift from mitochondrial fission to fusion; both mechanisms favor CKD progression in the remnant renal mass.

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