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19 pages, 8098 KiB

Open AccessArticle

Effects of Long-Term Physical Activity and BCAA Availability on the Subcellular Associations between Intramyocellular Lipids, Perilipins and PGC-1α

by Vasco Fachada, Mika Silvennoinen, Ulla-Maria Sahinaho, Paavo Rahkila, Riikka Kivelä, Juha J. Hulmi, Urho Kujala and Heikki Kainulainen

Int. J. Mol. Sci. 2023, 24(5), 4282; https://doi.org/10.3390/ijms24054282 - 21 Feb 2023

Viewed by 2590

Abstract

Cellular skeletal muscle lipid metabolism is of paramount importance for metabolic health, specifically through its connection to branched-chain amino acids (BCAA) metabolism and through its modulation by exercise. In this study, we aimed at better understanding intramyocellular lipids (IMCL) and their related key [...] Read more.

Cellular skeletal muscle lipid metabolism is of paramount importance for metabolic health, specifically through its connection to branched-chain amino acids (BCAA) metabolism and through its modulation by exercise. In this study, we aimed at better understanding intramyocellular lipids (IMCL) and their related key proteins in response to physical activity and BCAA deprivation. By means of confocal microscopy, we examined IMCL and the lipid droplet coating proteins PLIN2 and PLIN5 in human twin pairs discordant for physical activity. Additionally, in order to study IMCLs, PLINs and their association to peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1

α

) in cytosolic and nuclear pools, we mimicked exercise-induced contractions in C2C12 myotubes by electrical pulse stimulation (EPS), with or without BCAA deprivation. The life-long physically active twins displayed an increased IMCL signal in type I fibers when compared to their inactive twin pair. Moreover, the inactive twins showed a decreased association between PLIN2 and IMCL. Similarly, in the C2C12 cell line, PLIN2 dissociated from IMCL when myotubes were deprived of BCAA, especially when contracting. In addition, in myotubes, EPS led to an increase in nuclear PLIN5 signal and its associations with IMCL and PGC-1

α

. This study demonstrates how physical activity and BCAA availability affects IMCL and their associated proteins, providing further and novel evidence for the link between the BCAA, energy and lipid metabolisms. Full article

(This article belongs to the Special Issue Advances in Skeletal Muscle Function and Metabolism)

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18 pages, 5122 KiB

Open AccessArticle

Taurine Stimulates AMP-Activated Protein Kinase and Modulates the Skeletal Muscle Functions in Rats via the Induction of Intracellular Calcium Influx

by Baojun Sun, Hitomi Maruta, Yun Ma and Hiromi Yamashita

Int. J. Mol. Sci. 2023, 24(4), 4125; https://doi.org/10.3390/ijms24044125 - 18 Feb 2023

Cited by 3 | Viewed by 2487

Abstract

Taurine (2-aminoethanesulfonic acid) is a free amino acid abundantly found in mammalian tissues. Taurine plays a role in the maintenance of skeletal muscle functions and is associated with exercise capacity. However, the mechanism underlying taurine function in skeletal muscles has not yet been [...] Read more.

Taurine (2-aminoethanesulfonic acid) is a free amino acid abundantly found in mammalian tissues. Taurine plays a role in the maintenance of skeletal muscle functions and is associated with exercise capacity. However, the mechanism underlying taurine function in skeletal muscles has not yet been elucidated. In this study, to investigate the mechanism of taurine function in the skeletal muscles, the effects of short-term administration of a relatively low dose of taurine on the skeletal muscles of Sprague–Dawley rats and the underlying mechanism of taurine function in cultured L6 myotubes were investigated. The results obtained in this study in rats and L6 cells indicate that taurine modulates the skeletal muscle function by stimulating the expression of genes and proteins associated with mitochondrial and respiratory metabolism through the activation of AMP-activated protein kinase via the calcium signaling pathway. Full article

(This article belongs to the Special Issue Advances in Skeletal Muscle Function and Metabolism)

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20 pages, 4554 KiB

Open AccessArticle

miR-193b-3p Promotes Proliferation of Goat Skeletal Muscle Satellite Cells through Activating IGF2BP1

by Li Li, Xiao Zhang, Hailong Yang, Xiaoli Xu, Yuan Chen, Dinghui Dai, Siyuan Zhan, Jiazhong Guo, Tao Zhong, Linjie Wang, Jiaxue Cao and Hongping Zhang

Int. J. Mol. Sci. 2022, 23(24), 15760; https://doi.org/10.3390/ijms232415760 - 12 Dec 2022

Cited by 3 | Viewed by 2128

Abstract

As a well-known cancer-related miRNA, miR-193b-3p is enriched in skeletal muscle and dysregulated in muscle disease. However, the mechanism underpinning this has not been addressed so far. Here, we probed the impact of miR-193b-3p on myogenesis by mainly using goat tissues and skeletal [...] Read more.

As a well-known cancer-related miRNA, miR-193b-3p is enriched in skeletal muscle and dysregulated in muscle disease. However, the mechanism underpinning this has not been addressed so far. Here, we probed the impact of miR-193b-3p on myogenesis by mainly using goat tissues and skeletal muscle satellite cells (MuSCs), compared with mouse C2C12 myoblasts. miR-193b-3p is highly expressed in goat skeletal muscles, and ectopic miR-193b-3p promotes MuSCs proliferation and differentiation. Moreover, insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1) is the most activated insulin signaling gene when there is overexpression of miR-193b-3p; the miRNA recognition element (MRE) within the IGF1BP1 3′ untranslated region (UTR) is indispensable for its activation. Consistently, expression patterns and functions of IGF2BP1 were similar to those of miR-193b-3p in tissues and MuSCs. In comparison, ectopic miR-193b-3p failed to induce PAX7 expression and myoblast proliferation when there was IGF2BP1 knockdown. Furthermore, miR-193b-3p destabilized IGF2BP1 mRNA, but unexpectedly promoted levels of IGF2BP1 heteronuclear RNA (hnRNA), dramatically. Moreover, miR-193b-3p could induce its neighboring genes. However, miR-193b-3p inversely regulated IGF2BP1 and myoblast proliferation in the mouse C2C12 myoblast. These data unveil that goat miR-193b-3p promotes myoblast proliferation via activating IGF2BP1 by binding to its 3′ UTR. Our novel findings highlight the positive regulation between miRNA and its target genes in muscle development, which further extends the repertoire of miRNA functions. Full article

(This article belongs to the Special Issue Advances in Skeletal Muscle Function and Metabolism)

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21 pages, 4478 KiB

Open AccessArticle

Short-Term Mild Hypoxia Modulates Na,K-ATPase to Maintain Membrane Electrogenesis in Rat Skeletal Muscle

by Violetta V. Kravtsova, Arina A. Fedorova, Maria V. Tishkova, Alexandra A. Livanova, Viacheslav O. Matytsin, Viacheslav P. Ganapolsky, Oleg V. Vetrovoy and Igor I. Krivoi

Int. J. Mol. Sci. 2022, 23(19), 11869; https://doi.org/10.3390/ijms231911869 - 6 Oct 2022

Cited by 3 | Viewed by 1927

Abstract

The Na,K-ATPase plays an important role in adaptation to hypoxia. Prolonged hypoxia results in loss of skeletal muscle mass, structure, and performance. However, hypoxic preconditioning is known to protect against a variety of functional impairments. In this study, we tested the possibility of [...] Read more.

The Na,K-ATPase plays an important role in adaptation to hypoxia. Prolonged hypoxia results in loss of skeletal muscle mass, structure, and performance. However, hypoxic preconditioning is known to protect against a variety of functional impairments. In this study, we tested the possibility of mild hypoxia to modulate the Na,K-ATPase and to improve skeletal muscle electrogenesis. The rats were subjected to simulated high-altitude (3000 m above sea level) hypobaric hypoxia (HH) for 3 h using a hypobaric chamber. Isolated diaphragm and soleus muscles were tested. In the diaphragm muscle, HH increased the α2 Na,K-ATPase isozyme electrogenic activity and stably hyperpolarized the extrajunctional membrane for 24 h. These changes were accompanied by a steady increase in the production of thiobarbituric acid reactive substances as well as a decrease in the serum level of endogenous ouabain, a specific ligand of the Na,K-ATPase. HH also increased the α2 Na,K-ATPase membrane abundance without changing its total protein content; the plasma membrane lipid-ordered phase did not change. In the soleus muscle, HH protected against disuse (hindlimb suspension) induced sarcolemmal depolarization. Considering that the Na,K-ATPase is critical for maintaining skeletal muscle electrogenesis and performance, these findings may have implications for countermeasures in disuse-induced pathology and hypoxic therapy. Full article

(This article belongs to the Special Issue Advances in Skeletal Muscle Function and Metabolism)

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10 pages, 2145 KiB

Open AccessArticle

Effects of Maca on Muscle Hypertrophy in C2C12 Skeletal Muscle Cells

by Dong Yi, Maki Yoshikawa, Takeshi Sugimoto, Keigo Tomoo, Yoko Okada and Takeshi Hashimoto

Int. J. Mol. Sci. 2022, 23(12), 6825; https://doi.org/10.3390/ijms23126825 - 19 Jun 2022

Cited by 8 | Viewed by 4861

Abstract

With aging, sarcopenia and the associated locomotor disorders, have become serious problems. The roots of maca contain active ingredients (triterpenes) that have a preventive effect on sarcopenia. However, the effect of maca on muscle hypertrophy has not yet been investigated. The aim of [...] Read more.

With aging, sarcopenia and the associated locomotor disorders, have become serious problems. The roots of maca contain active ingredients (triterpenes) that have a preventive effect on sarcopenia. However, the effect of maca on muscle hypertrophy has not yet been investigated. The aim of this study was to examine the effects and mechanism of maca on muscle hypertrophy by adding different concentrations of yellow maca (0.1 mg/mL and 0.2 mg/mL) to C2C12 skeletal muscle cell culture. Two days after differentiation, maca was added for two days of incubation. The muscle diameter, area, differentiation index, and multinucleation, were assessed by immunostaining, and the expression levels of the proteins related to muscle protein synthesis/degradation were examined by Western blotting. Compared with the control group, the muscle diameter and area of the myotubes in the maca groups were significantly increased, and the cell differentiation index and multinucleation were significantly higher in the maca groups. Phosphorylation of Akt and mTOR was elevated in the maca groups. Maca also promoted the phosphorylation of AMPK. These results suggest that maca may promote muscle hypertrophy, differentiation, and maturation, potentially via the muscle hypertrophic signaling pathways such as Akt and mTOR, while exploring other pathways are needed. Full article

(This article belongs to the Special Issue Advances in Skeletal Muscle Function and Metabolism)

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15 pages, 2270 KiB

Open AccessArticle

High-Fat Diet Impairs Muscle Function and Increases the Risk of Environmental Heatstroke in Mice

by Matteo Serano, Cecilia Paolini, Antonio Michelucci, Laura Pietrangelo, Flavia A. Guarnier and Feliciano Protasi

Int. J. Mol. Sci. 2022, 23(9), 5286; https://doi.org/10.3390/ijms23095286 - 9 May 2022

Cited by 3 | Viewed by 3156

Abstract

Environmental heat-stroke (HS) is a life-threatening response often triggered by hot and humid weather. Several lines of evidence indicate that HS is caused by excessive heat production in skeletal muscle, which in turn is the result of abnormal Ca²⁺ leak from the [...] Read more.

Environmental heat-stroke (HS) is a life-threatening response often triggered by hot and humid weather. Several lines of evidence indicate that HS is caused by excessive heat production in skeletal muscle, which in turn is the result of abnormal Ca²⁺ leak from the sarcoplasmic reticulum (SR) and excessive production of oxidative species of oxygen and nitrogen. As a high fat diet is known to increase oxidative stress, the objective of the present study was to investigate the effects of 3 months of high-fat diet (HFD) on the HS susceptibility of wild type (WT) mice. HS susceptibility was tested in an environmental chamber where 4 months old WT mice were exposed to heat stress (41 °C for 1 h). In comparison with mice fed with a regular diet, mice fed with HFD showed: (a) increased body weight and accumulation of adipose tissue; (b) elevated oxidative stress in skeletal muscles; (c) increased heat generation and oxygen consumption during exposure to heat stress; and finally, (d) enhanced sensitivity to both temperature and caffeine of isolated muscles during in-vitro contracture test. These data (a) suggest that HFD predisposes WT mice to heat stress and (b) could have implications for guidelines regarding food intake during periods of intense environmental heat. Full article

(This article belongs to the Special Issue Advances in Skeletal Muscle Function and Metabolism)

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15 pages, 5130 KiB

Open AccessArticle

Effect of Long-Term Supplementation with Acetic Acid on the Skeletal Muscle of Aging Sprague Dawley Rats

by Hitomi Maruta, Reina Abe and Hiromi Yamashita

Int. J. Mol. Sci. 2022, 23(9), 4691; https://doi.org/10.3390/ijms23094691 - 23 Apr 2022

Cited by 8 | Viewed by 3496

Abstract

Mitochondrial function in skeletal muscle, which plays an essential role in oxidative capacity and physical activity, declines with aging. Acetic acid activates AMP-activated protein kinase (AMPK), which plays a key role in the regulation of whole-body energy by phosphorylating key metabolic enzymes in [...] Read more.

Mitochondrial function in skeletal muscle, which plays an essential role in oxidative capacity and physical activity, declines with aging. Acetic acid activates AMP-activated protein kinase (AMPK), which plays a key role in the regulation of whole-body energy by phosphorylating key metabolic enzymes in both biosynthetic and oxidative pathways and stimulates gene expression associated with slow-twitch fibers and mitochondria in skeletal muscle cells. In this study, we investigate whether long-term supplementation with acetic acid improves age-related changes in the skeletal muscle of aging rats in association with the activation of AMPK. Male Sprague Dawley (SD) rats were administered acetic acid orally from 37 to 56 weeks of age. Long-term supplementation with acetic acid decreased the expression of atrophy-related genes, such as atrogin-1, muscle RING-finger protein-1 (MuRF1), and transforming growth factor beta (TGF-β), activated AMPK, and affected the proliferation of mitochondria and type I fiber-related molecules in muscles. The findings suggest that acetic acid exhibits an anti-aging function in the skeletal muscles of aging rats. Full article

(This article belongs to the Special Issue Advances in Skeletal Muscle Function and Metabolism)

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16 pages, 2285 KiB

Open AccessArticle

Store-Operated Ca²⁺ Entry in Skeletal Muscle Contributes to the Increase in Body Temperature during Exertional Stress

by Barbara Girolami, Matteo Serano, Antonio Michelucci, Laura Pietrangelo and Feliciano Protasi

Int. J. Mol. Sci. 2022, 23(7), 3772; https://doi.org/10.3390/ijms23073772 - 29 Mar 2022

Cited by 4 | Viewed by 2709

Abstract

Exertional heat stroke (HS) is a hyperthermic crisis triggered by an excessive accumulation of Ca²⁺ in skeletal muscle fibers. We demonstrated that exercise leads to the formation of calcium entry units (CEUs), which are intracellular junctions that reduce muscle fatigue by promoting [...] Read more.

Exertional heat stroke (HS) is a hyperthermic crisis triggered by an excessive accumulation of Ca²⁺ in skeletal muscle fibers. We demonstrated that exercise leads to the formation of calcium entry units (CEUs), which are intracellular junctions that reduce muscle fatigue by promoting the recovery of extracellular Ca²⁺ via store-operated Ca²⁺ entry (SOCE). Here, we tested the hypothesis that exercise-induced assembly of CEUs may increase the risk of HS when physical activity is performed in adverse environmental conditions (high temperature and humidity). Adult mice were: (a) first, divided into three experimental groups: control, trained-1 month (voluntary running in wheel cages), and acutely exercised-1 h (incremental treadmill run); and (b) then subjected to an exertional stress (ES) protocol, a treadmill run in an environmental chamber at 34 °C and 40% humidity. The internal temperature of the mice at the end of the ES was higher in both pre-exercised groups. During an ES ex-vivo protocol, extensor digitorum longus(EDL) muscles from the trained-1 month and exercised-1 h mice generated greater basal tension than in the control and were those that contained a greater number of CEUs, assessed by electron microscopy. The data collected suggest that the entry of Ca²⁺ from extracellular space via CEUs could contribute to exertional HS when exercise is performed in adverse environmental conditions. Full article

(This article belongs to the Special Issue Advances in Skeletal Muscle Function and Metabolism)

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16 pages, 3881 KiB

Open AccessArticle

A Single Bout of Ultra-Endurance Exercise Reveals Early Signs of Muscle Aging in Master Athletes

by Cécile Coudy-Gandilhon, Marine Gueugneau, Christophe Chambon, Daniel Taillandier, Lydie Combaret, Cécile Polge, Guillaume Y. Millet, Léonard Féasson and Daniel Béchet

Int. J. Mol. Sci. 2022, 23(7), 3713; https://doi.org/10.3390/ijms23073713 - 28 Mar 2022

Cited by 4 | Viewed by 5063

Abstract

Middle-aged and master endurance athletes exhibit similar physical performance and long-term muscle adaptation to aerobic exercise. Nevertheless, we hypothesized that the short-term plasticity of the skeletal muscle might be distinctly altered for master athletes when they are challenged by a single bout of [...] Read more.

Middle-aged and master endurance athletes exhibit similar physical performance and long-term muscle adaptation to aerobic exercise. Nevertheless, we hypothesized that the short-term plasticity of the skeletal muscle might be distinctly altered for master athletes when they are challenged by a single bout of prolonged moderate-intensity exercise. Six middle-aged (37Y) and five older (50Y) master highly-trained athletes performed a 24-h treadmill run (24TR). Vastus lateralis muscle biopsies were collected before and after the run and assessed for proteomics, fiber morphometry, intramyocellular lipid droplets (LD), mitochondrial oxidative activity, extracellular matrix (ECM), and micro-vascularisation. Before 24TR, muscle fiber type morphometry, intramyocellular LD, oxidative activity, ECM and micro-vascularisation were similar between master and middle-aged runners. For 37Y runners, 24TR was associated with ECM thickening, increased capillary-to-fiber interface, and an 89% depletion of LD in type-I fibers. In contrast, for 50Y runners, 24TR did not alter ECM and capillarization and poorly depleted LDs. Moreover, an impaired succinate dehydrogenase activity and functional class scoring of proteomes suggested reduced oxidative phosphorylation post-24TR exclusively in 50Y muscle. Collectively, our data support that middle-aged and master endurance athletes exhibit distinct transient plasticity in response to a single bout of ultra-endurance exercise, which may constitute early signs of muscle aging for master athletes. Full article

(This article belongs to the Special Issue Advances in Skeletal Muscle Function and Metabolism)

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15 pages, 2987 KiB

Open AccessArticle

The Role of Glycogen Synthase Kinase-3 in the Regulation of Ribosome Biogenesis in Rat Soleus Muscle under Disuse Conditions

by Sergey V. Rozhkov, Kristina A. Sharlo, Boris S. Shenkman and Timur M. Mirzoev

Int. J. Mol. Sci. 2022, 23(5), 2751; https://doi.org/10.3390/ijms23052751 - 2 Mar 2022

Cited by 3 | Viewed by 2692

Abstract

It is well-established that prolonged exposure to real or simulated microgravity/disuse conditions results in a significant reduction in the rate of muscle protein synthesis (PS) and loss of muscle mass. Muscle protein synthesis is largely dependent upon translational capacity (ribosome content), the regulation [...] Read more.

It is well-established that prolonged exposure to real or simulated microgravity/disuse conditions results in a significant reduction in the rate of muscle protein synthesis (PS) and loss of muscle mass. Muscle protein synthesis is largely dependent upon translational capacity (ribosome content), the regulation of which is poorly explored under conditions of mechanical unloading. Glycogen synthase kinase-3 (GSK-3) (a negative regulator of PS) is known to be activated in rat soleus muscle under unloading conditions. We hypothesized that inhibition of GSK-3 activity under disuse conditions (hindlimb suspension, HS) would reduce disuse-induced downregulation of ribosome biogenesis in rat soleus muscle. Wistar rats were randomly divided into four groups: (1) vivarium control (C), (2) vivarium control + daily injections (4 mg/kg) of AR-A014418 (GSK-3 inhibitor) for 7 days, (3) 7-day HS, (4) 7-day HS + daily injections (4 mg/kg) of AR-A014418. GSK-3beta and glycogen synthase 1 (GS-1) phosphorylation levels were measured by Western-blotting. The key markers of ribosome biogenesis were assessed via agarose gel-electrophoresis and RT-PCR. The rate of muscle PS was assessed by puromycin-based SUnSET method. As expected, 7-day HS resulted in a significant decrease in the inhibitory Ser9 GSK-3beta phosphorylation and an increase in GS-1 (Ser641) phosphorylation compared to the C group. Treatment of rats with GSK-3 inhibitor prevented HS-induced increase in GS1 (Ser641) phosphorylation, which was indicative of GSK-3 inhibition. Administration of GSK-3 inhibitor partly attenuated disuse-induced downregulation of c-Myc expression as well as decreases in the levels of 45S pre-rRNA and 18S + 28S rRNAs. These AR-A014418-induced alterations in the markers of ribosome biogenesis were paralleled with partial prevention of a decrease in the rate of muscle PS. Thus, inhibition of GSK-3 during 7-day HS is able to partially attenuate the reductions in translational capacity and the rate of PS in rat soleus muscle. Full article

(This article belongs to the Special Issue Advances in Skeletal Muscle Function and Metabolism)

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19 pages, 1295 KiB

Open AccessArticle

Nitrite Concentration in the Striated Muscles Is Reversely Related to Myoglobin and Mitochondrial Proteins Content in Rats

by Joanna Majerczak, Agnieszka Kij, Hanna Drzymala-Celichowska, Kamil Kus, Janusz Karasinski, Zenon Nieckarz, Marcin Grandys, Jan Celichowski, Zbigniew Szkutnik, Ulrike B. Hendgen-Cotta and Jerzy A. Zoladz

Int. J. Mol. Sci. 2022, 23(5), 2686; https://doi.org/10.3390/ijms23052686 - 28 Feb 2022

Cited by 8 | Viewed by 2876

Abstract

Skeletal muscles are an important reservoir of nitric oxide (NO^•) stored in the form of nitrite [NO₂⁻] and nitrate [NO₃⁻] (NO_x). Nitrite, which can be reduced to NO^• under hypoxic and acidotic [...] Read more.

Skeletal muscles are an important reservoir of nitric oxide (NO^•) stored in the form of nitrite [NO₂⁻] and nitrate [NO₃⁻] (NO_x). Nitrite, which can be reduced to NO^• under hypoxic and acidotic conditions, is considered a physiologically relevant, direct source of bioactive NO^•. The aim of the present study was to determine the basal levels of NO_x in striated muscles (including rat heart and locomotory muscles) with varied contents of tissue nitrite reductases, such as myoglobin and mitochondrial electron transport chain proteins (ETC-proteins). Muscle NO_x was determined using a high-performance liquid chromatography-based method. Muscle proteins were evaluated using western-immunoblotting. We found that oxidative muscles with a higher content of ETC-proteins and myoglobin (such as the heart and slow-twitch locomotory muscles) have lower [NO₂⁻] compared to fast-twitch muscles with a lower content of those proteins. The muscle type had no observed effect on the [NO₃⁻]. Our results demonstrated that fast-twitch muscles possess greater potential to generate NO^• via nitrite reduction than slow-twitch muscles and the heart. This property might be of special importance for fast skeletal muscles during strenuous exercise and/or hypoxia since it might support muscle blood flow via additional NO^• provision (acidic/hypoxic vasodilation) and delay muscle fatigue. Full article

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19 pages, 3355 KiB

Open AccessArticle

Astaxanthin Exerts Anabolic Effects via Pleiotropic Modulation of the Excitable Tissue

by Mónika Gönczi, Andrea Csemer, László Szabó, Mónika Sztretye, János Fodor, Krisztina Pocsai, Kálmán Szenthe, Anikó Keller-Pintér, Zoltán Márton Köhler, Péter Nánási, Norbert Szentandrássy, Balázs Pál and László Csernoch

Int. J. Mol. Sci. 2022, 23(2), 917; https://doi.org/10.3390/ijms23020917 - 14 Jan 2022

Cited by 2 | Viewed by 2280

Abstract

Astaxanthin is a lipid-soluble carotenoid influencing lipid metabolism, body weight, and insulin sensitivity. We provide a systematic analysis of acute and chronic effects of astaxanthin on different organs. Changes by chronic astaxanthin feeding were analyzed on general metabolism, expression of regulatory proteins in [...] Read more.

Astaxanthin is a lipid-soluble carotenoid influencing lipid metabolism, body weight, and insulin sensitivity. We provide a systematic analysis of acute and chronic effects of astaxanthin on different organs. Changes by chronic astaxanthin feeding were analyzed on general metabolism, expression of regulatory proteins in the skeletal muscle, as well as changes of excitation and synaptic activity in the hypothalamic arcuate nucleus of mice. Acute responses were also tested on canine cardiac muscle and different neuronal populations of the hypothalamic arcuate nucleus in mice. Dietary astaxanthin significantly increased food intake. It also increased protein levels affecting glucose metabolism and fatty acid biosynthesis in skeletal muscle. Inhibitory inputs innervating neurons of the arcuate nucleus regulating metabolism and food intake were strengthened by both acute and chronic astaxanthin treatment. Astaxanthin moderately shortened cardiac action potentials, depressed their plateau potential, and reduced the maximal rate of depolarization. Based on its complex actions on metabolism and food intake, our data support the previous findings that astaxanthin is suitable for supplementing the diet of patients with disturbances in energy homeostasis. Full article

(This article belongs to the Special Issue Advances in Skeletal Muscle Function and Metabolism)

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14 pages, 2850 KiB

Open AccessArticle

VEGFB Promotes Myoblasts Proliferation and Differentiation through VEGFR1-PI3K/Akt Signaling Pathway

by Mingfa Ling, Lulu Quan, Xumin Lai, Limin Lang, Fan Li, Xiaohua Yang, Yiming Fu, Shengchun Feng, Xin Yi, Canjun Zhu, Ping Gao, Xiaotong Zhu, Lina Wang, Gang Shu, Qingyan Jiang and Songbo Wang

Int. J. Mol. Sci. 2021, 22(24), 13352; https://doi.org/10.3390/ijms222413352 - 12 Dec 2021

Cited by 28 | Viewed by 4498

Abstract

It has been demonstrated that vascular endothelial growth factor B (VEGFB) plays a vital role in regulating vascular biological function. However, the role of VEGFB in regulating skeletal muscle cell proliferation and differentiation remains unclear. Thus, this study aimed to investigate the effects [...] Read more.

It has been demonstrated that vascular endothelial growth factor B (VEGFB) plays a vital role in regulating vascular biological function. However, the role of VEGFB in regulating skeletal muscle cell proliferation and differentiation remains unclear. Thus, this study aimed to investigate the effects of VEGFB on C2C12 myoblast proliferation and differentiation and to explore the underlying mechanism. For proliferation, VEGFB significantly promoted the proliferation of C2C12 myoblasts with the upregulating expression of cyclin D1 and PCNA. Meanwhile, VEGFB enhanced vascular endothelial growth factor receptor 1 (VEGFR1) expression and activated the PI3K/Akt signaling pathway in a VEGFR1-dependent manner. In addition, the knockdown of VEGFR1 and inhibition of PI3K/Akt totally abolished the promotion of C2C12 proliferation induced by VEGFB, suggesting that VEGFB promoted C2C12 myoblast proliferation through the VEGFR1-PI3K/Akt signaling pathway. Regarding differentiation, VEGFB significantly stimulated the differentiation of C2C12 myoblasts via VEGFR, with elevated expressions of MyoG and MyHC. Furthermore, the knockdown of VEGFR1 rather than NRP1 eliminated the VEGFB-stimulated C2C12 differentiation. Moreover, VEGFB activated the PI3K/Akt/mTOR signaling pathway in a VEGFR1-dependent manner. However, the inhibition of PI3K/Akt/mTOR blocked the promotion of C2C12 myoblasts differentiation induced by VEGFB, indicating the involvement of the PI3K/Akt pathway. To conclude, these findings showed that VEGFB promoted C2C12 myoblast proliferation and differentiation via the VEGFR1-PI3K/Akt signaling pathway, providing new insights into the regulation of skeletal muscle development. Full article

(This article belongs to the Special Issue Advances in Skeletal Muscle Function and Metabolism)

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22 pages, 447 KiB

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Many Ways to Rome: Exercise, Cold Exposure and Diet—Do They All Affect BAT Activation and WAT Browning in the Same Manner?

by Anna K. Scheel, Lena Espelage and Alexandra Chadt

Int. J. Mol. Sci. 2022, 23(9), 4759; https://doi.org/10.3390/ijms23094759 - 26 Apr 2022

Cited by 31 | Viewed by 6455

Abstract

The discovery of functional brown adipose tissue (BAT) in adult humans and the possibility to recruit beige cells with high thermogenic potential within white adipose tissue (WAT) depots opened the field for new strategies to combat obesity and its associated comorbidities. Exercise training [...] Read more.

The discovery of functional brown adipose tissue (BAT) in adult humans and the possibility to recruit beige cells with high thermogenic potential within white adipose tissue (WAT) depots opened the field for new strategies to combat obesity and its associated comorbidities. Exercise training as well as cold exposure and dietary components are associated with the enhanced accumulation of metabolically-active beige adipocytes and BAT activation. Both activated beige and brown adipocytes increase their metabolic rate by utilizing lipids to generate heat via non-shivering thermogenesis, which is dependent on uncoupling protein 1 (UCP1) in the inner mitochondrial membrane. Non-shivering thermogenesis elevates energy expenditure and promotes a negative energy balance, which may ameliorate metabolic complications of obesity and Type 2 Diabetes Mellitus (T2DM) such as insulin resistance (IR) in skeletal muscle and adipose tissue. Despite the recent advances in pharmacological approaches to reduce obesity and IR by inducing non-shivering thermogenesis in BAT and WAT, the administered pharmacological compounds are often associated with unwanted side effects. Therefore, lifestyle interventions such as exercise, cold exposure, and/or specified dietary regimens present promising anchor points for future disease prevention and treatment of obesity and T2DM. The exact mechanisms where exercise, cold exposure, dietary interventions, and pharmacological treatments converge or rather diverge in their specific impact on BAT activation or WAT browning are difficult to determine. In the past, many reviews have demonstrated the mechanistic principles of exercise- and/or cold-induced BAT activation and WAT browning. In this review, we aim to summarize not only the current state of knowledge on the various mechanistic principles of diverse external stimuli on BAT activation and WAT browning, but also present their translational potential in future clinical applications. Full article

(This article belongs to the Special Issue Advances in Skeletal Muscle Function and Metabolism)

15 pages, 1824 KiB

Open AccessReview

Stem Cell and Macrophage Roles in Skeletal Muscle Regenerative Medicine

by Pasqualina Scala, Laura Rehak, Valentina Giudice, Elena Ciaglia, Annibale Alessandro Puca, Carmine Selleri, Giovanna Della Porta and Nicola Maffulli

Int. J. Mol. Sci. 2021, 22(19), 10867; https://doi.org/10.3390/ijms221910867 - 8 Oct 2021

Cited by 31 | Viewed by 4973

Abstract

In severe muscle injury, skeletal muscle tissue structure and functionality can be repaired through the involvement of several cell types, such as muscle stem cells, and innate immune responses. However, the exact mechanisms behind muscle tissue regeneration, homeostasis, and plasticity are still under [...] Read more.

In severe muscle injury, skeletal muscle tissue structure and functionality can be repaired through the involvement of several cell types, such as muscle stem cells, and innate immune responses. However, the exact mechanisms behind muscle tissue regeneration, homeostasis, and plasticity are still under investigation, and the discovery of pathways and cell types involved in muscle repair can open the way for novel therapeutic approaches, such as cell-based therapies involving stem cells and peripheral blood mononucleate cells. Indeed, peripheral cell infusions are a new therapy for muscle healing, likely because autologous peripheral blood infusion at the site of injury might enhance innate immune responses, especially those driven by macrophages. In this review, we summarize current knowledge on functions of stem cells and macrophages in skeletal muscle repairs and their roles as components of a promising cell-based therapies for muscle repair and regeneration. Full article

(This article belongs to the Special Issue Advances in Skeletal Muscle Function and Metabolism)

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