Dietary short-term supplementation of grape seed proanthocyanidin extract improves pork quality and promotes skeletal muscle fiber type conversion in finishing pigs.

Plant extracts are commonly used as feed additives to improve pork quality. However, due to their high cost, shortening the duration of supplement use can help reduce production costs. In this study, we aimed to investigate the effects of grape seed proanthocyanidin extract (GSPE) on meat quality and muscle fiber characteristics of finishing pigs during the late stage of fattening, which was 30 days in our experimental design. The results indicated that short-term dietary supplementation of GSPE significantly reduced backfat thickness, but increased loin eye area and improved meat color and tenderness. Moreover, GSPE increased slow myosin heavy chain (MyHC) expression and malate dehydrogenase (MDH) activity, while decreasing fast MyHC expression and lactate dehydrogenase (LDH) activity in the Longissimus thoracis (LT) muscle. Additionally, GSPE increased the expression of Sirt1 and PGC-1α proteins in the LT muscle of finishing pigs and upregulated AMP-activated protein kinase α 1 (AMPKα1), AMPKα2, nuclear respiratory factor 1 (NRF1), and calcium/calmodulin-dependent protein kinase kinase ß (CaMKKß) mRNA expression levels. These findings suggest that even during the late stage of fattening, GSPE treatment can regulate skeletal muscle fiber type transformation through the AMPK signaling pathway, thereby affecting the muscle quality of finishing pigs. Therefore, by incorporating GSPE into the diet of pigs during the late stage of fattening, producers can enhance pork quality while reducing production costs.

Dietary Taurine Supplementation Improves the Meat Quality, Muscle Fiber Type, and Mitochondrial Function of Finishing Pigs.

This study investigated the effects of dietary supplementation with taurine (TAU) on the meat quality, muscle fiber type, and mitochondrial function of finishing pigs. The results demonstrated that TAU significantly increased the a* value while decreasing b*45 min, L*24 h, and drip loss24 h and drip loss48 h in the longissimus dorsi (LD) muscle. Dietary supplemented with TAU reduced the content of lactate and the glycolytic potential (GP) in the LD muscle. Dietary supplemented with TAU enhanced the oxidative fiber-related gene expression as well as increased succinic dehydrogenase and malate dehydrogenase activities while reducing lactate dehydrogenase activity. Furthermore, dietary supplementation with TAU increased the contents of mtDNA and ATP and mitochondrial function-related gene expression. Moreover, TAU enhanced the mRNA expressions of calcineurin (CaN) and nuclear factor of activated T cells c1 (NFATc1) and protein expressions of CNA and NFATc1. The results indicate that dietary TAU supplementation improves meat quality and mitochondrial biogenesis and function and promotes muscle fiber-type conversion from the glycolytic fiber to the oxidative fiber via the CaN/NFATc1 pathway.

FHL3 promotes the formation of fast glycolytic muscle fibers by interacting with YY1 and muscle glycolytic metabolism.

The proportions of the various muscle fiber types are important in the regulation of skeletal muscle metabolism, as well as animal meat production. Four-and-a-half LIM domain protein 3 (FHL3) is highly expressed in fast glycolytic muscle fibers and differentially regulates the expression of myosin heavy chain (MyHC) isoforms at the cellular level. Whether FHL3 regulates the transformation of muscle fiber types in vivo and the regulatory mechanism is unclear. In this study, muscle-specific FHL3 transgenic mice were generated by random integration, and lentivirus-mediated gene knockdown or overexpression in muscles of mice or pigs was conducted. Functional analysis showed that overexpression of FHL3 in muscles significantly increased the proportion of fast-twitch myofibers and muscle mass but decreased muscle succinate dehydrogenase (SDH) activity and whole-body oxygen consumption. Lentivirus-mediated FHL3 knockdown in muscles significantly decreased muscle mass and the proportion of fast-twitch myofibers. Mechanistically, FHL3 directly interacted with the Yin yang 1 (YY1) DNA-binding domain, repressed the binding of YY1 to the fast glycolytic MyHC2b gene regulatory region, and thereby promoted MyHC2b expression. FHL3 also competed with EZH2 to bind the repression domain of YY1 and reduced H3K27me3 enrichment in the MyHC2b regulatory region. Moreover, FHL3 overexpression reduced glucose tolerance by affecting muscle glycolytic metabolism, and its mRNA expression in muscle was positively associated with hemoglobin A1c (HbA1c) in patients with type 2 diabetes. Therefore, FHL3 is a novel potential target gene for the treatment of muscle metabolism-related diseases and improvement of animal meat production.

Effects of dietary l-theanine supplementation on pork quality and muscle fiber type transformation in finishing pigs.

BACKGROUND: This experiment aimed to investigate effects of dietary l-theanine supplementation on pork quality and muscle fiber type transformation in finishing pigs. In a 30-day experiment, 18 healthy Duroc × Landrace × Yorkshire (DLY) pigs with an average body weight of 86.03 ± 0.83 kg were randomly divided into three groups (a basal diet or a basal diet supplemented with 500 and 1000 ppm l-theanine, respectively), with six duplicates and one pig per replicate. RESULTS: The results showed that dietary 1000 ppm l-theanine supplementation significantly reduced (P < 0.05) b*24 h and drip loss. Dietary 1000 ppm l-theanine supplementation significantly increased (P < 0.05) slow myosin heavy chain (MyHC) protein expression and the percentage of slow-twitch fibers, as well as significantly decreased (P < 0.05) fast MyHC protein expression and the percentage of fast-twitch fibers, accompanied by an increase in succinate dehydrogenase (SDH) and malate dehydrogenase (MDH) activities and a decrease in lactate dehydrogenase (LDH) activity. In addition, the adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway was activated by l-theanine. CONCLUSION: Together, this study demonstrated for the first time that dietary supplementation of 1000 ppm l-theanine can improve pork color and drip loss and promote muscle fiber type transformation from fast-twitch to slow-twitch in finishing pigs. © 2022 Society of Chemical Industry.

Dietary α-lipoic acid supplementation improves postmortem color stability of the lamb muscles through changing muscle fiber types and antioxidative status.

This study investigated the effect of dietary α-lipoic acid (600 mg/kg) supplementation on the postmortem color stability of the biceps femoris from lambs. The results showed that dietary α-lipoic acid supplementation increased a* and decreased b* and metmyoglobin (MMb) percentage of the biceps femoris with the time of storage (P < 0.05). The content of malondialdehyde (MDA) reduced with the time of storage after treatment with α-lipoic acid (P < 0.05). α-lipoic acid increased the myoglobin (Mb) content, and myosin heavy chain I (MyHC I) gene expression but decreased glycogen content, lactate dehydrogenase (LDH) activity, and MyHC IIb gene expression (P < 0.05). The T-AOC value, catalase (CAT) activity, and expression of SOD and CAT gene expression increased after α-lipoic acid treatment (P < 0.05). Therefore, dietary α-lipoic acid supplementation improved the meat color by regulating muscle fiber types and inhibited glycolysis. Moreover, α-lipoic acid maintained meat color stability by effectively inhibiting muscle oxidation via enhancing the antioxidant capacity.

Effect of dietary L-theanine supplementation on skeletal muscle fiber type transformation in weaning piglets.

The aim of this study was to explore the effect of dietary L-theanine (LT) supplementation on skeletal muscle fiber type transformation in weaning piglets. Our data showed that LT significantly increased the slow-twitch fiber-related genes expression and the percentage of slow oxidative fiber, and decreased the MyHC IIb mRNA expression and the percentage of fast glycolytic fiber. In addition, LT significantly increased the succinic dehydrogenase (SDH) and malate dehydrogenase (MDH) activities and increased the LDH activities. In addition, LT significantly affected mitochondrial biogenesis and function and antioxidative related genes expression, and increased the protein expression of p-adenosine monophosphate (AMP)-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), nuclear factor E2-related factor 2 (Nrf2), NADPH quinone oxidoreductase-1 (NQO1) and heme oxygenase-1 (HO-1) and decreased the Keap1 protein levels. Furthermore, our data indicated that LT significantly increased the mRNA and protein expression of prospero-related homeobox 1 (Prox1), calcineurin A (CnA), and NFATc1, suggesting that dietary LT supplementation promoted skeletal muscle fiber transition from types II to I might be via activation of calcineurin signaling pathway. Taken together, these findings suggested that LT promoted the transformation of muscle fiber types from slow oxidative to fast glycolytic by increasing antioxidant capacity and improving mitochondrial biogenesis and function and activation of calcineurin signaling pathway.

Effect of dietary dihydromyricetin supplementation on lipid metabolism, antioxidant capacity and skeletal muscle fiber type transformation in mice.

This study aimed to investigate the effect of dietary dihydromyricetin (DHM) supplementation on lipid metabolism, antioxidant capacity and muscle fiber type transformation. Twenty-four male Kunming mice were randomly allotted to either control (basal diet) or DHM diets (supplemented with 300 mg/kg DHM). Our data showed that DHM administration decreased the triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) contents, and increased the catalase (CAT), total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) activities in serum. In the liver, DHM decreased the TG and malondialdehyde (MDA) levels and increased the T-SOD and GSH-Px activities. For the tibialis anterior (TA) muscle, DHM increased the total antioxidant capacity (T-AOC) level and T-SOD activities. Western blotting and real-time quantitative PCR analysis showed that DHM increased the protein and mRNA levels of MyHC I and MyHC IIa and decreased the protein and mRNA levels of MyHC IIb in TA muscle, which may be achieved by activating the AMP-activated protein kinase (AMPK) signal. The mRNA levels of several regulatory factors related to mitochondrial function were up-regulated by DHM. In conclusion, dietary 300 mg/kg DHM supplementation improved lipid metabolism and antioxidant capacity and promoted the transformation of muscle fiber type from glycolysis to oxidation in mice.

Effect of dietary leucine supplementation on skeletal muscle fiber type transformation in weaning piglets.

To investigate the effects of dietary leucine supplementation on muscle fiber type transformation in weaning piglets, 54 21-day-old male DLY (Duroc × Landrace × Yorkshire) weaned piglets were randomly divided into control, 0.25% and 0.5% leucine groups. The experiment lasted for 42 d. The results showed that dietary supplementation of 0.25% leucine significantly increased the protein expressions of slow MyHC, myoglobin and Troponin I-SS and the mRNA expressions of MyHC I, MyHC IIa, Tnni1, Tnnc1, Tnnt1 and myoglobin, while decreased the protein level of fast MyHC and the mRNA level of MyHC IIb in longissimus dorsi (LD) muscle. Furthermore, 0.25% leucine significantly increased succinic dehydrogenase (SDH) activity and decreased lactate dehydrogenase (LDH) activity. In addition, our data found that 0.25% leucine significantly increased serum adiponectin (AdipoQ) concentration, and the protein levels of AdipoQ, adiponectin receptor 1 (AdipoR1), phosphorylated AMP-activated protein kinase (p-AMPK) and PPAR-γ coactivator-1α (PGC-1α) and the mRNA levels of AdipoQ, AdipoR1 and AMPKα2. Together, our findings indicate that leucine promotes porcine skeletal muscle fiber type transformation from fast-twitch to slow-twitch, and the effect may be mediated by AdipoQ-AMPK-PGC-1α signaling pathway.

Balanced branched-chain amino acids modulate meat quality by adjusting muscle fiber type conversion and intramuscular fat deposition in finishing pigs.

BACKGROUND: Pork is an important food for humans and improving the quality of pork is closely related to human health. This study was designed to investigate the effects of balanced branched-chain amino acid (BCAA)-supplemented protein-restricted diets on meat quality, muscle fiber types, and intramuscular fat (IMF) in finishing pigs. RESULTS: The results showed that, compared with the normal protein diet (160 g kg-1 crude protein), the reduced-protein diet (120 g kg-1 crude protein) supplemented with BCAAs to the ratio of 2:1:2 not only had higher average daily gain (P < 0.05) and carcass weight (P < 0.05) but also improved meat tenderness and juiciness by decreasing shear force (P < 0.05) and increasing water-holding capacity (P < 0.05). In particular, this treatment showed higher (P < 0.05) levels of phospho-acetyl-CoA carboxylase (P-ACC) and peroxisome proliferation-activated receptor-γ (PPARγ), and lower (P < 0.05) levels of P-adenosine 5'-monophosphate (AMP)-activated protein kinase (P-AMPK), increasing the composition of IMF and MyHC I (P < 0.05) in the longissimus dorsi muscle (LDM). In terms of health, this group increased eicosapentaenoic acid (EPA) (P < 0.01) and desirable hypocholesterolemic fatty acids (DHFA) (P < 0.05), and decreased atherogenicity (AI) (P < 0.01) and hypercholesterolemic saturated fatty acids (HSFA) (P < 0.05). CONCLUSION: Our findings suggest a novel role for a balanced BCAA-supplemented restricted protein (RP) diet in the epigenetic regulation of more tender and healthier pork by increasing IMF deposition and fiber type conversion, providing a cross-regulatory molecular basis for revealing the nutritional regulation network of meat quality. © 2021 Society of Chemical Industry.

Naringin induces skeletal muscle fiber type transformation via AMPK/PGC-1α signaling pathway in mice and C2C12 myotubes.

A large number of studies have shown that polyphenols can regulate skeletal muscle fiber type transformation through AMPK signal. However, the effects and mechanism of naringin (a natural polyphenol) on muscle fiber type transformation still remains unclear. Thus, we hypothesized that naringin would induce the transformation of skeletal muscle fibers from type II to type I by AMPK signaling. C2C12 myotubes and BALB/c mice models were used to test this hypothesis. We found that naringin significantly increased the protein expression of slow myosin heavy chain (MyHC), myoglobin and troponin I type I slow skeletal (Troponin I-SS) and the activities of succinate dehydrogenase (SDH) and malate dehydrogenase (MDH), and significantly decreased fast MyHC protein expression and lactate dehydrogenase (LDH) activity, accompanied by the activation of AMPK and the activity of peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α) in mice and C2C12 myotubes. Further inhibition of AMPK activity by compound C showed that the above effects were significantly inhibited in C2C12 myotubes. In conclusion, naringin promotes the transformation of skeletal muscle fibers from type II to type I through AMPK/PGC-1α signaling pathway, which not only enriches the nutritional and physiological functions of naringin, but also provides a theoretical basis for the regulation of muscle fiber type transformation by nutritional approaches.

Effects of dietary ferulic acid supplementation on growth performance and skeletal muscle fiber type conversion in weaned piglets.

BACKGROUND: Ferulic acid (FA) is a common polyphenolic compound. The purpose of this study was to explore the effect of dietary FA supplementation on growth performance and muscle fiber type conversion in weaned piglets. In this study, eighteen 21-day-old DLY (Duroc × Landrace × Yorkshire) weaned piglets were randomly divided into control, 0.05% FA, and 0.45% FA groups. RESULTS: Our study showed that dietary FA supplementation had no effect on growth performance, but it could upregulate the expression of slow myosin heavy chain (MyHC) protein, increase the activities of succinic dehydrogenase and malate dehydrogenase, and downregulate the expression of fast MyHC protein. Dietary FA supplementation also increased the expression levels of phosphorylated AMP-activated protein kinase, sirtuin 1 (Sirt1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), myocyte enhancer factor 2C, and troponin I-SS, increased the proportion of slow-twitch fiber, and decreased the proportion of fast-twitch fiber. In addition, our results showed that dietary FA supplementation increased the messenger RNA abundance of mitochondrial nuclear transcription genes, including ATP synthase membrane subunit c locus 1, cytochrome oxidase subunit 1, nuclear respiratory factor 1, mitochondrial transcription factor A, mitochondrial transcription factor B1, and cytochrome c. CONCLUSION: We provided the first evidence that FA could promote muscle fiber type conversion from fast-twitch to slow-twitch via the Sirt1/AMP-activated protein kinase/PGC-1α signaling pathway and could improve the mitochondrial function in weaned piglets. This means that FA can be used as a dietary supplement to improve the quality of pork. © 2021 Society of Chemical Industry.

Effects of apple polyphenols on myofiber-type transformation in longissimus dorsi muscle of finishing pigs.

This study aimed to investigate effects of apple polyphenols (APPs) on myofiber-type transformation in longissimus dorsi muscle of finishing pigs and its mechanism. In this study, 36 healthy castrated Duroc × Landrace × Yorkshire pigs with an average body weight of 71.25 ± 2.40 kg were randomly divided into three treatment groups (control, 0.04% APPs, 0.08% APPs). The experiment lasted for 49 days. Results showed that dietary APP supplementation increased the protein expression of MyHC I and the activities of succinic dehydrogenase and malate dehydrogenase, as well as decreased the protein expression of MyHC IIb and the activity of lactate dehydrogenase, suggesting that APPs promoted muscle fiber-type transformation from fast-twitch to slow-twitch in finishing pigs. We also showed that dietary 0.08% APP supplementation increased the expressions of mitochondrial biogenesis and function-related proteins PGC-1α, Sirt1 and Cytc. In addition, dietary supplementation with 0.08% APPs increased the activities of T-SOD, GSH-PX and CAT and decreased the MDA content. Together, we provided the first evidence that APP promotes muscle fiber-type transformation from fast-twitch to slow-twitch in finishing pigs, which may be achieved by improving the mitochondrial biogenesis and function and increasing the antioxidant capacity of skeletal muscle.

Oral L-glutamine pretreatment attenuates skeletal muscle atrophy induced by 24-h fasting in mice.

L-Glutamine (L-Gln) supplementation has been pointed out as an anticatabolic intervention, but its effects on protein synthesis and degradation signaling in skeketal muscle are still poorly known. The effects of L-Gln pretreatment (1 g kg-1 day-1 body weight for 10 days) on muscle fiber cross-sectional area (CSA), amino acid composition (measured by LC-MS/MS) and protein synthesis (Akt-mTOR) and degradation (ubiquitin ligases) signaling in soleus and extensor digitorum longus (EDL) muscles in 24-h-fasted mice were investigated. The fiber CSA of EDL muscle was not different between the L-Gln-fasted and L-Gln-fed groups. This finding was associated with reduced contents of L-Leu and L-Iso and activation of protein synthesis signaling (p-RPS6Ser240/244 and Akt-mTOR). The spectrum of soleus muscle fiber CSA distribution was larger in L-Gln-fasted as compared with placebo-fasted mice. This effect of L-Gln pretreatment was associated with changes in red fibers L-Gln metabolism as indicated by increased intracellular L-glutamine/L-glutamate ratio, L-aspartate and GABA levels. L-Gln supplementation reduced fasting-induced mass loss in tibialis anterior and gastrocnemius muscles. Evidence is presented that pretreatment with L-glutamine attenuates skeletal muscle atrophy induced by 24-h fasting through mechanisms that vary with the muscle fiber type.

Increase in muscle endurance in mice by dietary Yamabushitake mushroom (Hericium erinaceus) possibly via activation of PPARδ.

Skeletal muscle fiber is largely classified into two types: type 1 (slow-twitch) and type 2 (fast-twitch) fibers. Meat quality and composition of fiber types are thought to be closely related. Previous research showed that overexpression of constitutively active peroxisome proliferator-activated receptor (PPAR)δ, a nuclear receptor present in skeletal muscle, increased type 1 fibers in mice. In this study, we found that hexane extracts of Yamabushitake mushroom (Hericium erinaceus) showed PPARδ agonistic activity in vitro. Eight-week-old C57BL/6J mice were fed a diet supplemented with 5% (w/w) freeze-dried Yamabushitake mushroom for 24 hr. After the treatment period, the extensor digitorum longus (EDL) muscles were excised. The Yamabushitake-supplemented diet up-regulated the PPARδ target genes Pdk4 and Ucp3 in mouse skeletal muscles in vivo. Furthermore, feeding the Yamabushitake-supplemented diet to mice for 8 weeks resulted in a significant increase in muscle endurance. These results indicate that Yamabushitake mushroom contains PPARδ agonistic ligands and that dietary intake of Yamabushitake mushroom could activate PPARδ in skeletal muscle of mice. Unexpectedly, we observed no significant alterations in composition of muscle fiber types between the mice fed control and Yamabushitake-supplemented diets.

[Effect of electroacupuncture on amyotrophia and expression of myogenic differentiation-related genes of gastrocnemius in rats with chronic constriction injury of sciatic nerve].

OBJECTIVE: To explore the effect of electroacupuncture(EA) on amyotrophia and expression of paired box7(Pax7), myogenic differentiation antigen-1 (Myod1), myogenin (Myog), myosin heavy chain- Ⅱa (Myh2), myosin heavy chain-Ⅱx (Myh1) and myosin heavy chain-Ⅰ (Myh7) of denervated gastrocnemius in rats with chronic constriction injury (CCI) of the right sciatic nerve, so as to explore its mechanisms underlying postponing development of amyotrophia. METHODS: Sixty-six SD adult male rats were randomly divided into sham operation (sham) group (n＝24), model group (n＝24) and EA group (n＝18). The denervated muscle (gastrocnemius) atrophy model was established by CCI of the right sciatic nerve. EA (2 Hz，1.0 mA) was applied to the right "Zusanli"(ST36) and "Huantiao"(GB30) for 10 min, once a day, six times a week and for 1, 2 and 4 weeks, respectively. After complete dissection of bilateral gastrocnemius muscles, their wet weight levels were measured and the ratio of wet weight (＝that of the operation side/that of the non-operation side) was calculated, and the cross-sectional area (CSA) and diameter of the gastronemius were detected after fixation in 4% paraformaldehyde, sectioning, and H．E. staining. The expression levels of Pax7, Myod1, Myog, Myh2, Myh1 and Myh7 mRNAs in the gastrocnemius tissue after 3 weeks of modeling were detected with quantitative real time-PCR (qPCR). RESULTS: After 1 week of modeling, the ratios of wet weight of gastrocnemius and the CSA and fiber diameter at the 2nd, 3rd and 5th week were significantly smaller in the model group than in the sham group (P<0.05). The expression levels of Myod1 and Myog mRNAs were significantly up-regulated (P<0.01), and those of Myh2, Myh1 and Myh7 considerably down-regulated in the model group compared with the sham group (P<0.05, P<0.01). No significant changes were found in the expression levels of Pax7 mRNA after modeling and EA intervention (P>0.05)．Following EA intervention, the CSA and diameterof the gastronemius were obviously increased (P<0.05), and the expression levels of Myod1, Myog and Myh7 further markedly or remarkably up-regulated in comparison with the model group (P<0.05, P<0.01). No significant changes were found in the ratio of wet weight of gastrocnemius at the 3 time-points, and the expression levels of Myh2 mRNA and Myh1 mRNA in the EA group relevant to the model group after 3 weeks of modeling (P>0.05). CONCLUSION: EA treatment may delay gastrocnemius atrophy in CCI rats, which is possibly associated with its effects in up-regulating the expression of Myod1, Myog and Myh7 mRNAs to control the differentiation of the satellite cells and the muscle fiber type transformation.

Arginine promotes skeletal muscle fiber type transformation from fast-twitch to slow-twitch via Sirt1/AMPK pathway.

This study investigated the effect of arginine on skeletal muscle fiber type transformation in mice and in C2C12 myotubes. Our data showed that dietary supplementation of arginine in mice significantly up-regulated the slow myosin heavy chain (MyHC), troponin I-SS, sirtuin1 (Sirt1) and peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α) protein expressions, as well as significantly down-regulated the fast MyHC protein expression. In C2C12 myotubes, arginine significantly increased the protein level of slow MyHC and the number of slow MyHC-positive cells, as well as significantly decreased the protein level of fast MyHC and the number of fast MyHC-positive cells. We also showed that arginine increased the activities of succinic dehydrogenase and malate dehydrogenase and decreased the activity of lactate dehydrogenase in mice and in C2C12 myotubes. Here we found that AMP-activated protein kinase (AMPK) was activated by arginine in mice and in C2C12 myotubes. However, inhibition of AMPK activity by compound C significantly attenuated the effects of arginine on slow MyHC and fast MyHC expressions in C2C12 myotubes. Finally, we showed that inhibition of Sirt1 expression by EX527 attenuated arginine-induced increase in the protein levels of phospho-AMPK and slow MyHC, the mRNA level of nitric oxide synthase (NOS) and the contents of NOS and NO, as well as decrease in fast MyHC protein level. Together, our findings indicated that arginine promotes skeletal muscle fiber type switching from fast-twitch to slow-twitch via Sirt1/AMPK pathway.

The regulation of skeletal muscle fiber-type composition by betaine is associated with NFATc1/MyoD.

Increasing evidence indicates that muscular dysfunction or alterations in skeletal muscle fiber-type composition not only are involved in muscle metabolism and function but also can limit functional capacity. Therefore, understanding the mechanisms regulating key events during skeletal myogenesis is necessary. Betaine is a naturally occurring component of commonly eaten foods. Here, we showed that 10 mM betaine supplementation in vitro significantly repressed myoblast proliferation and enhanced myoblast differentiation. This effect can be mediated by regulation of miR-29b-3p. Further analysis showed that betaine supplementation in vitro regulated skeletal muscle fiber-type composition through the induction of NFATc1 and the negative regulation of MyoD expression. Furthermore, mice fed with 10 mM betaine in water for 133 days showed no impairment in overall health. Consistently, betaine supplementation increased muscle mass, promoted muscle formation, and modulated the ratio of fiber types in skeletal muscle in vivo. These findings shed light on the diverse biological functions of betaine and indicate that betaine supplementation may lead to new therapies for diseases such as muscular dystrophy or other diseases related to muscle dysfunction. KEY MESSAGES: Betaine supplementation inhibits proliferation and promotes differentiation of C2C12 myoblasts. Betaine supplementation regulates fast to slow muscle fiber-type conversion and is associated with NFATc1/MyoD. Betaine supplementation enhances skeletal myogenesis in vivo. Betaine supplementation does not impair health of mice.

Unloading-induced atrophy and decreased oxidative capacity of the soleus muscle in rats are reversed by pre- and postconditioning with mild hyperbaric oxygen.

Our aim was to determine the effects of pre- and/or postconditioning with mild hyperbaric oxygen (1.25 atmospheric pressure, 36% oxygen for 3 h/day) on the properties of the soleus muscle that was atrophied by hindlimb suspension-induced unloading. Twelve groups of 8-week-old rats were housed under normobaric conditions (1 atmospheric pressure, 20.9% oxygen) or exposed to mild hyperbaric oxygen for 2 weeks. Ten groups then were housed under normobaric conditions for 2 weeks with their hindlimbs either unloaded via suspension or not unloaded. Six groups subsequently were either housed under normobaric conditions or exposed to mild hyperbaric oxygen for 2 weeks: the suspended groups were allowed to recover under reloaded conditions (unrestricted normal cage activity). Muscle weights, cross-sectional areas of all fiber types, oxidative capacity (muscle succinate dehydrogenase activity and fiber succinate dehydrogenase staining intensity) decreased, and a shift of fibers from type I to type IIA and type IIC was observed after hindlimb unloading. In addition, mRNA levels of peroxisome proliferator-activated receptor γ coactivator-1α decreased, whereas those of forkhead box-containing protein O1 increased after hindlimb unloading. Muscle atrophy and decreased oxidative capacity were unaffected by either pre- or postconditioning with mild hyperbaric oxygen. In contrast, these changes were followed by a return to nearly normal levels after 2 weeks of reloading when pre- and postconditioning were combined. Therefore, a combination of pre- and postconditioning with mild hyperbaric oxygen can be effective against the atrophy and decreased oxidative capacity of skeletal muscles associated with hindlimb unloading.

High-phosphorus diet maximizes and low-dose calcitriol attenuates skeletal muscle changes in long-term uremic rats.

Although disorders of mineral metabolism and skeletal muscle are common in chronic kidney disease (CKD), their potential relationship remains unexplored. Elevations in plasma phosphate, parathyroid hormone, and fibroblastic growth factor 23 together with decreased calcitriol levels are common features of CKD. High-phosphate intake is a major contributor to progression of CKD. This study was primarily aimed to determine the influence of high-phosphate intake on muscle and to investigate whether calcitriol supplementation counteracts negative skeletal muscle changes associated with long-term uremia. Proportions and metabolic and morphological features of myosin-based muscle fiber types were assessed in the slow-twitch soleus and the fast-twitch tibialis cranialis muscles of uremic rats (5/6 nephrectomy, Nx) and compared with sham-operated (So) controls. Three groups of Nx rats received either a standard diet (0.6% phosphorus, Nx-Sd), or a high-phosphorus diet (0.9% phosphorus, Nx-Pho), or a high-phosphorus diet plus calcitriol (10 ng/kg 3 day/wk ip, Nx-Pho + Cal) for 12 wk. Two groups of So rats received either a standard diet or a high-phosphorus diet (So-Pho) over the same period. A multivariate analysis encompassing all fiber-type characteristics indicated that Nx-Pho + Cal rats displayed skeletal muscle phenotypes intermediate between Nx-Pho and So-Pho rats and that uremia-induced skeletal muscle changes were of greater magnitude in Nx-Pho than in Nx-Sd rats. In uremic rats, treatment with calcitriol preserved fiber-type composition, cross-sectional size, myonuclear domain size, oxidative capacity, and capillarity of muscle fibers. These data demonstrate that a high-phosphorus diet potentiates and low-dose calcitriol attenuates adverse skeletal muscle changes in long-term uremic rats.