Obesity is associated with skeletal muscle mass loss and physical dysfunction.Krill oil(KO)has been shown to be beneficial in human health.However,the effect of KO on obesity-induced skeletal muscle atrophy is still u...Obesity is associated with skeletal muscle mass loss and physical dysfunction.Krill oil(KO)has been shown to be beneficial in human health.However,the effect of KO on obesity-induced skeletal muscle atrophy is still unclear.In this study,the male C57BL/6J mice were fed a high-fat diet(HFD)for 12 weeks to induce obesity,and then were intragastric administration with 400 mg/kg bw KO for an additional 6 weeks.The results showed that KO treatment reduced body weight,fat accumulation and serum pro-inflammatory cytokines in HFD-induced obese mice.Importantly,KO treatment attenuated skeletal muscle atrophy in HFD-fed mice,as evidenced by preserving skeletal muscle mass,average myofiber cross-sectional area and grip strength.KO administration also mitigated obesity-induced ectopic lipid deposition and inflammatory response in skeletal muscle.Additionally,KO treatment inhibited the transcriptional activities of nuclear factor-κB(NF-κB)p65 and forkhead box O 3a(FoxO3a),and then down-regulated muscle atrophy F-box(MAFbx)and muscle-specific RING finger protein 1(MuRF1)protein levels in skeletal muscle from HFD-fed mice.KO administration also improved obesity-induced impaired muscle protein synthesis via activating PI3K/Akt pathway.Furthermore,KO treatment enhanced muscle mitochondrial biogenesis in HFD-induced obese mice via activating PGC-1αpathway.Collectively,KO might be developed as a potential nutritional supplement for the prevention and treatment of obesity-induced skeletal muscle atrophy.展开更多
Over the course of several decades,robust research has firmly established the significance of mitochondrial pathology as a central contributor to the onset of skeletal muscle atrophy in individuals with diabetes.Howev...Over the course of several decades,robust research has firmly established the significance of mitochondrial pathology as a central contributor to the onset of skeletal muscle atrophy in individuals with diabetes.However,the specific intricacies governing this process remain elusive.Extensive evidence highlights that individuals with diabetes regularly confront the severe consequences of skeletal muscle degradation.Deciphering the sophisticated mechanisms at the core of this pathology requires a thorough and meticulous exploration into the nuanced factors intricately associated with mitochondrial dysfunction.展开更多
As a key coordinator of metabolism,AMP-activated protein kinase(AMPK)is vitally involved in skeletal muscle maintenance.AMPK exerts its cellular effects through its function as a serine/threonine protein kinase by reg...As a key coordinator of metabolism,AMP-activated protein kinase(AMPK)is vitally involved in skeletal muscle maintenance.AMPK exerts its cellular effects through its function as a serine/threonine protein kinase by regulating many downstream targets and plays important roles in the development and growth of skeletal muscle.AMPK is activated by phosphorylation and exerts its function as a kinase in many processes,including synthesis and degradation of proteins,mitochondrial biogenesis,glucose uptake,and fatty acid and cholesterol metabolism.Skeletal muscle atrophy is a result of various diseases or disorders and is characterized by a decrease in muscle mass.The pathogenesis and therapeutic strategies of skeletal muscle atrophy are still under investigation.In this review,we discuss the role of AMPK in skeletal muscle metabolism and atrophy.We also discuss targeting AMPK for skeletal muscle treatment,including exercise,AMPK activators including 5-amino-4-imidazolecarboxamide ribonucleoside and metformin,and low-level lasers.These studies show the important roles of AMPK in regulating muscle metabolism and function;thus,the treatment of skeletal muscle atrophy needs to take into account the roles of AMPK.展开更多
Background and Objective:Cachexia-induced skeletal muscle atrophy is a critical manifestation in Kirsten rat sarcoma viral oncogene homologue(KRAS)-mutant pancreatic cancer(PC)patients,predominantly characterized by a...Background and Objective:Cachexia-induced skeletal muscle atrophy is a critical manifestation in Kirsten rat sarcoma viral oncogene homologue(KRAS)-mutant pancreatic cancer(PC)patients,predominantly characterized by a shift in metabolic equilibrium towards catabolism that accelerates protein degradation in myofibers and leads to muscle atrophy.This metabolic reprogramming not only supports tumor growth but also precipitates energy depletion in skeletal muscle tissues.Exploring these mechanisms reveals potential therapeutic targets in the metabolic and proteolytic pathways associated with KRAS-mutant PC.Methods:A comprehensive search for literature was conducted in PubMed,Web of Science,Google Scholar and other search engines up to May 21st,2024.Studies on PC models and patients were included.Key Content and Findings:The crosstalk between KRAS-mutant PC and skeletal muscle atrophy can be categorized into four principal domains:(I)KRAS-driven metabolic reprogramming in cancer cells leads to the depletion of muscle energy reserves,thereby influencing the reallocation of myofiber energy towards fueling cancer cell;(Ⅱ)KRAS-mutant cancer cells rely on nutrient-scavenging pathways,resulting in altered cytokine profiles,increased ubiquitin mRNA expression and autophagy-lysosome pathway,which facilitate myotube degradation and inhibit muscle regeneration,thereby disrupting muscular homeostasis and causing a one-way nutrient flux;(Ⅲ)tumor-induced oxidative stress inflicts damage on myotubes,highlighting the detrimental effects of reactive oxygen species on muscle structure;(Ⅳ)KRAS-mutant cancer cells remodulate immune cell dynamics within the tumor environment,thereby reshaping host immunity.Together,these findings illuminate the intricate interplay between KRAS-mutant PC and skeletal muscle atrophy,mapping the pathophysiological framework that is crucial for understanding sarcopenia and related disorders.Conclusions:This comprehensive analysis advances our understanding of the complex etiology of cancer cachexia and stimulates the development of targeted therapeutic strategies.展开更多
Skeletal muscle atrophy inevitably occurs in denervated skeletal muscle, and cell apoptosis plays an important role in skeletal muscle atrophy and degeneration. The present study established rat models of simple nerve...Skeletal muscle atrophy inevitably occurs in denervated skeletal muscle, and cell apoptosis plays an important role in skeletal muscle atrophy and degeneration. The present study established rat models of simple nerve injury by transecting the ventral or dorsal spinal nerve root and observed rat skeletal muscle cell apoptosis following simple motor nerve injury versus simple sensory nerve injury. Following skeletal muscle denervation for 10 weeks, cell apoptosis was detected in skeletal muscle, which was accompanied by obvious changes in rat behavior and electrophysiological responses. In addition, changes in cross-sectional area and average gray-scale of motor endplates of the gastrocnemius muscle were analyzed following sciatic nerve injury and motor nerve injury. Cell nuclei in denervated skeletal muscle tissue were more densely arranged than in normal skeletal muscle tissue. Cell nuclei were most dense in the sciatic nerve injury group, followed by the motor nerve injury group and the sensory nerve injury group. Fas/FasL expression and the number of apoptotic cells increased in denervated skeletal muscle, and apoptosis-related changes were observed. These findings suggested that motor and sensory nerves provided trophic actions following skeletal muscle and motor nerve injury, resulting in a greater influence on skeletal muscle atrophy than sensory nerve injury. Therefore, reconstruction of motor nerves should be preferentially considered for treating denervation-induced skeletal muscle atrophy.展开更多
Peripheral nerve injuries commonly occur due to trauma,like a traffic accident.Peripheral nerves get severed,causing motor neuron death and potential muscle atrophy.The current golden standard to treat peripheral nerv...Peripheral nerve injuries commonly occur due to trauma,like a traffic accident.Peripheral nerves get severed,causing motor neuron death and potential muscle atrophy.The current golden standard to treat peripheral nerve lesions,especially lesions with large(≥3 cm)nerve gaps,is the use of a nerve autograft or reimplantation in cases where nerve root avulsions occur.If not tended early,degeneration of motor neurons and loss of axon regeneration can occur,leading to loss of function.Although surgical procedures exist,patients often do not fully recover,and quality of life deteriorates.Peripheral nerves have limited regeneration,and it is usually mediated by Schwann cells and neurotrophic factors,like glial cell line-derived neurotrophic factor,as seen in Wallerian degeneration.Glial cell line-derived neurotrophic factor is a neurotrophic factor known to promote motor neuron survival and neurite outgrowth.Glial cell line-derived neurotrophic factor is upregulated in different forms of nerve injuries like axotomy,sciatic nerve crush,and compression,thus creating great interest to explore this protein as a potential treatment for peripheral nerve injuries.Exogenous glial cell line-derived neurotrophic factor has shown positive effects in regeneration and functional recovery when applied in experimental models of peripheral nerve injuries.In this review,we discuss the mechanism of repair provided by Schwann cells and upregulation of glial cell line-derived neurotrophic factor,the latest findings on the effects of glial cell line-derived neurotrophic factor in different types of peripheral nerve injuries,delivery systems,and complementary treatments(electrical muscle stimulation and exercise).Understanding and overcoming the challenges of proper timing and glial cell line-derived neurotrophic factor delivery is paramount to creating novel treatments to tend to peripheral nerve injuries to improve patients'quality of life.展开更多
Endurance exercise training promotes a protective phenotype in skeletal muscle known as exercise pre-conditioning.Exercise preconditioning protects muscle fibers against a variety of threats including inactivity-induc...Endurance exercise training promotes a protective phenotype in skeletal muscle known as exercise pre-conditioning.Exercise preconditioning protects muscle fibers against a variety of threats including inactivity-induced muscle atrophy.The mechanism(s)responsible for exercise preconditioning remain unknown and are explored in these experiments.Specifically,we investigated the impact of endurance exercise training on key components of the renin-angiotensin system(RAS).The RAS was targeted because activation of the classical axis of the RAS pathway via angiotensinⅡtypeⅠreceptors(AT1Rs)promotes muscle atrophy whereas activation of the non-classical RAS axis via Mas receptors(MasRs)inhibits the atrophic signaling of the classical RAS pathway.Guided by prior studies,we hypothesized that an exercise-induced decrease in AT1Rs and/or increases in MasRs in skeletal muscle fibers is a potential mechanism responsible for exercise preconditioning.Following endurance exercise training in rats,we examined the abundance of AT1Rs and MasRs in both locomotor and respiratory muscles.Our results indicate that endurance exercise training does not alter the protein abundance of AT1Rs or MasRs in muscle fibers from the diaphragm,plantaris,and soleus muscles compared to sedentary controls(p>0.05).Furthermore,fluorescent angiotensinⅡ(AngⅡ)binding analyses confirm our results that exercise pre-conditioning does not alter the protein abundance of AT1Rs in the diaphragm,plantaris,and soleus(p>0.05).This study confirms that exercise-induced changes in RAS receptors are not a key mechanism that contributes to the beneficial effects of exercise preconditioning in skeletal muscle fibers.展开更多
基金supported by the National Natural Science Foundation of China(82003447,32202023)the Natural Science Foundation of Shandong Province(ZR2021QC177)the Young Scholars Program of Shandong University(2018WLJH33,2018WLJH34)。
文摘Obesity is associated with skeletal muscle mass loss and physical dysfunction.Krill oil(KO)has been shown to be beneficial in human health.However,the effect of KO on obesity-induced skeletal muscle atrophy is still unclear.In this study,the male C57BL/6J mice were fed a high-fat diet(HFD)for 12 weeks to induce obesity,and then were intragastric administration with 400 mg/kg bw KO for an additional 6 weeks.The results showed that KO treatment reduced body weight,fat accumulation and serum pro-inflammatory cytokines in HFD-induced obese mice.Importantly,KO treatment attenuated skeletal muscle atrophy in HFD-fed mice,as evidenced by preserving skeletal muscle mass,average myofiber cross-sectional area and grip strength.KO administration also mitigated obesity-induced ectopic lipid deposition and inflammatory response in skeletal muscle.Additionally,KO treatment inhibited the transcriptional activities of nuclear factor-κB(NF-κB)p65 and forkhead box O 3a(FoxO3a),and then down-regulated muscle atrophy F-box(MAFbx)and muscle-specific RING finger protein 1(MuRF1)protein levels in skeletal muscle from HFD-fed mice.KO administration also improved obesity-induced impaired muscle protein synthesis via activating PI3K/Akt pathway.Furthermore,KO treatment enhanced muscle mitochondrial biogenesis in HFD-induced obese mice via activating PGC-1αpathway.Collectively,KO might be developed as a potential nutritional supplement for the prevention and treatment of obesity-induced skeletal muscle atrophy.
基金the Foundation of State Key Laboratory of Component-based Chinese Medicine,No.CBCM2023107National Natural Science Foundation of China,No.81901853Specially Funded Scientific Research Project of the Fourth Affiliated Hospital of Harbin Medical University,No.HYDSYTB202126.
文摘Over the course of several decades,robust research has firmly established the significance of mitochondrial pathology as a central contributor to the onset of skeletal muscle atrophy in individuals with diabetes.However,the specific intricacies governing this process remain elusive.Extensive evidence highlights that individuals with diabetes regularly confront the severe consequences of skeletal muscle degradation.Deciphering the sophisticated mechanisms at the core of this pathology requires a thorough and meticulous exploration into the nuanced factors intricately associated with mitochondrial dysfunction.
基金supported by the Natural Science Foundation of China(Grant No.32071517,82072106)the Natural Science Basic Research Plan in Shaanxi Province of China(Grant No.2020JM-100).
文摘As a key coordinator of metabolism,AMP-activated protein kinase(AMPK)is vitally involved in skeletal muscle maintenance.AMPK exerts its cellular effects through its function as a serine/threonine protein kinase by regulating many downstream targets and plays important roles in the development and growth of skeletal muscle.AMPK is activated by phosphorylation and exerts its function as a kinase in many processes,including synthesis and degradation of proteins,mitochondrial biogenesis,glucose uptake,and fatty acid and cholesterol metabolism.Skeletal muscle atrophy is a result of various diseases or disorders and is characterized by a decrease in muscle mass.The pathogenesis and therapeutic strategies of skeletal muscle atrophy are still under investigation.In this review,we discuss the role of AMPK in skeletal muscle metabolism and atrophy.We also discuss targeting AMPK for skeletal muscle treatment,including exercise,AMPK activators including 5-amino-4-imidazolecarboxamide ribonucleoside and metformin,and low-level lasers.These studies show the important roles of AMPK in regulating muscle metabolism and function;thus,the treatment of skeletal muscle atrophy needs to take into account the roles of AMPK.
基金supported by grants from the Shanghai Municipal Health Commission Health Industry Clinical Research Project(No.201940019)National Natural Science Foundation of China(Nos.82273382,82272929,82103409,81972218,81972257,and 81827807)+5 种基金Shanghai ShenKang Hospital Development Centre Project(No.SHDC2020CR2017B)Program of Shanghai Academic/Technology Research Leader(No.23XD1400600)China Postdoctoral Science Foundation(No.2021M690037)Shanghai Sailing Program(No.21YF1407100),the Open Fund of the Key Laboratory of Hepatosplenic Surgery,Ministry of Education,Harbin,China(No.GPKF202302)Beijing Xisike Clinical Oncology Research Foundation(Nos.Y-2022METAZQN-0003,Y-HR2022MS-0251,and Y-HR2022QN-0085)Science and Technology Planning Project of Yunnan Province(No.202305AF150148).
文摘Background and Objective:Cachexia-induced skeletal muscle atrophy is a critical manifestation in Kirsten rat sarcoma viral oncogene homologue(KRAS)-mutant pancreatic cancer(PC)patients,predominantly characterized by a shift in metabolic equilibrium towards catabolism that accelerates protein degradation in myofibers and leads to muscle atrophy.This metabolic reprogramming not only supports tumor growth but also precipitates energy depletion in skeletal muscle tissues.Exploring these mechanisms reveals potential therapeutic targets in the metabolic and proteolytic pathways associated with KRAS-mutant PC.Methods:A comprehensive search for literature was conducted in PubMed,Web of Science,Google Scholar and other search engines up to May 21st,2024.Studies on PC models and patients were included.Key Content and Findings:The crosstalk between KRAS-mutant PC and skeletal muscle atrophy can be categorized into four principal domains:(I)KRAS-driven metabolic reprogramming in cancer cells leads to the depletion of muscle energy reserves,thereby influencing the reallocation of myofiber energy towards fueling cancer cell;(Ⅱ)KRAS-mutant cancer cells rely on nutrient-scavenging pathways,resulting in altered cytokine profiles,increased ubiquitin mRNA expression and autophagy-lysosome pathway,which facilitate myotube degradation and inhibit muscle regeneration,thereby disrupting muscular homeostasis and causing a one-way nutrient flux;(Ⅲ)tumor-induced oxidative stress inflicts damage on myotubes,highlighting the detrimental effects of reactive oxygen species on muscle structure;(Ⅳ)KRAS-mutant cancer cells remodulate immune cell dynamics within the tumor environment,thereby reshaping host immunity.Together,these findings illuminate the intricate interplay between KRAS-mutant PC and skeletal muscle atrophy,mapping the pathophysiological framework that is crucial for understanding sarcopenia and related disorders.Conclusions:This comprehensive analysis advances our understanding of the complex etiology of cancer cachexia and stimulates the development of targeted therapeutic strategies.
基金Clinical Scientific Research Foundation Project of Nantong University,No. 200626
文摘Skeletal muscle atrophy inevitably occurs in denervated skeletal muscle, and cell apoptosis plays an important role in skeletal muscle atrophy and degeneration. The present study established rat models of simple nerve injury by transecting the ventral or dorsal spinal nerve root and observed rat skeletal muscle cell apoptosis following simple motor nerve injury versus simple sensory nerve injury. Following skeletal muscle denervation for 10 weeks, cell apoptosis was detected in skeletal muscle, which was accompanied by obvious changes in rat behavior and electrophysiological responses. In addition, changes in cross-sectional area and average gray-scale of motor endplates of the gastrocnemius muscle were analyzed following sciatic nerve injury and motor nerve injury. Cell nuclei in denervated skeletal muscle tissue were more densely arranged than in normal skeletal muscle tissue. Cell nuclei were most dense in the sciatic nerve injury group, followed by the motor nerve injury group and the sensory nerve injury group. Fas/FasL expression and the number of apoptotic cells increased in denervated skeletal muscle, and apoptosis-related changes were observed. These findings suggested that motor and sensory nerves provided trophic actions following skeletal muscle and motor nerve injury, resulting in a greater influence on skeletal muscle atrophy than sensory nerve injury. Therefore, reconstruction of motor nerves should be preferentially considered for treating denervation-induced skeletal muscle atrophy.
基金funded by the NIH Grant 1R15AG022908-01A2 and the Western Michigan University(to JMS)。
文摘Peripheral nerve injuries commonly occur due to trauma,like a traffic accident.Peripheral nerves get severed,causing motor neuron death and potential muscle atrophy.The current golden standard to treat peripheral nerve lesions,especially lesions with large(≥3 cm)nerve gaps,is the use of a nerve autograft or reimplantation in cases where nerve root avulsions occur.If not tended early,degeneration of motor neurons and loss of axon regeneration can occur,leading to loss of function.Although surgical procedures exist,patients often do not fully recover,and quality of life deteriorates.Peripheral nerves have limited regeneration,and it is usually mediated by Schwann cells and neurotrophic factors,like glial cell line-derived neurotrophic factor,as seen in Wallerian degeneration.Glial cell line-derived neurotrophic factor is a neurotrophic factor known to promote motor neuron survival and neurite outgrowth.Glial cell line-derived neurotrophic factor is upregulated in different forms of nerve injuries like axotomy,sciatic nerve crush,and compression,thus creating great interest to explore this protein as a potential treatment for peripheral nerve injuries.Exogenous glial cell line-derived neurotrophic factor has shown positive effects in regeneration and functional recovery when applied in experimental models of peripheral nerve injuries.In this review,we discuss the mechanism of repair provided by Schwann cells and upregulation of glial cell line-derived neurotrophic factor,the latest findings on the effects of glial cell line-derived neurotrophic factor in different types of peripheral nerve injuries,delivery systems,and complementary treatments(electrical muscle stimulation and exercise).Understanding and overcoming the challenges of proper timing and glial cell line-derived neurotrophic factor delivery is paramount to creating novel treatments to tend to peripheral nerve injuries to improve patients'quality of life.
基金the National Institute of Health(R21AR063956 to SKP).
文摘Endurance exercise training promotes a protective phenotype in skeletal muscle known as exercise pre-conditioning.Exercise preconditioning protects muscle fibers against a variety of threats including inactivity-induced muscle atrophy.The mechanism(s)responsible for exercise preconditioning remain unknown and are explored in these experiments.Specifically,we investigated the impact of endurance exercise training on key components of the renin-angiotensin system(RAS).The RAS was targeted because activation of the classical axis of the RAS pathway via angiotensinⅡtypeⅠreceptors(AT1Rs)promotes muscle atrophy whereas activation of the non-classical RAS axis via Mas receptors(MasRs)inhibits the atrophic signaling of the classical RAS pathway.Guided by prior studies,we hypothesized that an exercise-induced decrease in AT1Rs and/or increases in MasRs in skeletal muscle fibers is a potential mechanism responsible for exercise preconditioning.Following endurance exercise training in rats,we examined the abundance of AT1Rs and MasRs in both locomotor and respiratory muscles.Our results indicate that endurance exercise training does not alter the protein abundance of AT1Rs or MasRs in muscle fibers from the diaphragm,plantaris,and soleus muscles compared to sedentary controls(p>0.05).Furthermore,fluorescent angiotensinⅡ(AngⅡ)binding analyses confirm our results that exercise pre-conditioning does not alter the protein abundance of AT1Rs in the diaphragm,plantaris,and soleus(p>0.05).This study confirms that exercise-induced changes in RAS receptors are not a key mechanism that contributes to the beneficial effects of exercise preconditioning in skeletal muscle fibers.
