bims-glecem 2022-03-13 papers

bims-glecem

Biomed News

on Glycogen metabolism in exercise, cancer and energy metabolism

Issue of 2022–03–13
twenty-one papers selected by
Dipsikha Biswas, Københavns Universitet

First report of suspected glycogen storage disease type 1a occurring in an adult dog.
The Role of Glycogen Synthase Kinase-3 in the Regulation of Ribosome Biogenesis in Rat Soleus Muscle under Disuse Conditions.
Consistency and Synchronization of AMPK-Glycogen in Endometrial Epithelial Cells is Critical to the Embryo Implantation.
Effects of Thiamin Restriction on Exercise-Associated Glycogen Metabolism and AMPK Activation Level in Skeletal Muscle.
A Non-Degradative Extraction Method for Molecular Structure Characterization of Bacterial Glycogen Particles.
Non-specificity of symptoms in infantile-onset Pompe disease may delay the diagnosis and institution of treatment.
The Role of IL-6 Released During Exercise to Insulin Sensitivity and Muscle Hypertrophy.
Anti-Fatigue and Exercise Performance Improvement Effect of Glossogyne tenuifolia Extract in Mice.
Scaling of fibre area and fibre glycogen concentration in the hindlimb musculature of monitor lizards: implications for locomotor performance with increasing body size.
Physical loading in professional soccer players: Implications for contemporary guidelines to encompass carbohydrate periodization.
d-Allulose Improves Endurance and Recovery from Exhaustion in Male C57BL/6J Mice.
HOIL-1 ubiquitin ligase activity targets unbranched glucosaccharides and is required to prevent polyglucosan accumulation.
Role of polyphenols in combating Type 2 Diabetes and insulin resistance.
Linc-RAM promotes muscle cell differentiation via regulating glycogen phosphorylase activity.
Nanoparticle Delivery Platforms for RNAi Therapeutics Targeting COVID-19 Disease in the Respiratory Tract.
New Opportunities to Advance the Field of Sports Nutrition.
Bioimpedance Phase Angle as a Prognostic Tool in Late-Onset Pompe Disease: A Single-Centre Prospective Study With a 15-year Follow-Up.
Hypoglycemic and hypolipidemic effects of polysaccharide isolated from Sphacelotheca sorghi in diet-streptozotocin-induced T2D mice.
Characterisation of breast cancer molecular signature and treatment assessment with vibrational spectroscopy and chemometric approach.
miR-378 affects metabolic disturbances in the mdx model of Duchenne muscular dystrophy.
High prevalence of CsRV2 in cultured Callinectes danae: Potential impacts on soft-shell crab production in Brazil.

J Small Anim Pract. 2022 Mar 10.

First report of suspected glycogen storage disease type 1a occurring in an adult dog.

K E Rolph, S M Cavanaugh, H E Wilson.

A 4-year-old female border collie was presented with haemoabdomen following the rupture of a hepatocellular carcinoma. After referral for ongoing elevation of alanine aminotransferase and alkaline phosphatase, the dog was found to have marked vacuolar hepatopathy due to glycogen accumulation within the liver, fasting hypoglycaemia and hyperlactataemia, and a negative response to glucagon stimulation testing. These changes were strongly suggestive of glycogen storage disease type 1a. Based on our literature search, this report documents the first adult canine to be diagnosed with suspected glycogen storage disease type 1a.

DOI: https://doi.org/10.1111/jsap.13494
Int J Mol Sci. 2022 Mar 02. pii: 2751. [Epub ahead of print]23(5):

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

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

  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.

Keywords:  18S rRNA; 28S rRNA; GSK-3; c-Myc; hindlimb unloading; muscle protein synthesis; ribosome biogenesis; simulated microgravity; soleus muscle

DOI:  https://doi.org/10.3390/ijms23052751
Reproduction. 2022 Mar 01. pii: REP-21-0382. [Epub ahead of print]

Consistency and Synchronization of AMPK-Glycogen in Endometrial Epithelial Cells is Critical to the Embryo Implantation.

Li Nie, Li-Xue Zhang, Yi-Cheng Wang, Yun Long, Yong-Dan Ma, Lin-Chuan Liao, Xin-Hua Dai, Zhi-Hui Cui, Huan Liu, Zhaoqi Wang, Ziyang Ma, Dongzhi Yuan, Li-Min Yue.

Uterine receptivity to the embryo is crucial for successful implantation. The establishment of uterine receptivity requires a large amount of energy, and abnormal energy regulation causes implantation failure. Glucose metabolism in the endometrium is tissue specific. Glucose is largely stored in the form of glycogen, which is the main energy source for the endometrium. AMP-activated protein kinase (AMPK), an important energy-sensing molecule, is a key player in the regulation of glucose metabolism, and its regulation is also tissue specific. However, the mechanism of energy regulation in the endometrium for the establishment of uterine receptivity remains to be elucidated. In this research, we aimed to investigate the energy regulation mechanism of mouse uterine receptivity and its significance in embryo implantation. The results showed that the AMPK, p-AMPK, glycogen synthase 1, and glycogen phosphorylase M levels and the glycogen content in mouse endometrial epithelium varied in a periodic manner under regulation by the ovarian hormone. Specifically, progesterone significantly activated AMPK, promoted glycogenolysis, and upregulated glycogen phosphorylase M expression. AMPK regulated glycogen phosphorylase M expression and promoted glycogenolysis. AMPK was also found to be activated by changes in the energy or glycogen of the endometrial epithelial cells. The inhibition of AMPK activity or glycogenolysis altered the uterine receptivity markers during the window of implantation and ultimately interfered with implantation. In summary, consistency and synchronization of AMPK and glycogen metabolism constitute the core regulatory mechanism in mouse endometrial epithelial cells involved in the establishment of uterine receptivity.

DOI: https://doi.org/10.1530/REP-21-0382
Nutrients. 2022 Feb 08. pii: 710. [Epub ahead of print]14(3):

Effects of Thiamin Restriction on Exercise-Associated Glycogen Metabolism and AMPK Activation Level in Skeletal Muscle.

Akiko Sato, Shinji Sato, Go Omori, Keiichi Koshinaka.

  This study aimed to investigate the direct influence of a decrease in the cellular thiamin level, before the onset of anorexia (one of the symptoms of thiamin deficiency) on glycogen metabolism and the AMP-activated protein kinase (AMPK) activation levels in skeletal muscle at rest and in response to exercise. Male Wistar rats were classified as the control diet (CON) group or the thiamin-deficient diet (TD) group and consumed the assigned diets for 1 week. Skeletal muscles were taken from the rats at rest, those that underwent low-intensity swimming (LIS), or high-intensity intermittent swimming (HIS) conducted immediately before dissection. There were no significant differences in food intake, locomotive activity, or body weight between groups, but thiamin pyrophosphate in the skeletal muscles of the TD group was significantly lower than that of the CON group. Muscle glycogen and lactate levels in the blood and muscle were equivalent between groups at rest and in response to exercise. The mitochondrial content was equal between groups, and AMPK in the skeletal muscles of TD rats was normally activated by LIS and HIS. In conclusion, with a lowered cellular thiamin level, the exercise-associated glycogen metabolism and AMPK activation level in skeletal muscle were normally regulated.

Keywords:  AMP-activated protein kinase (AMPK); exercise; glycogen; mitochondrial content; thiamin

DOI:  https://doi.org/10.3390/nu14030710
J Vis Exp. 2022 Feb 18.

A Non-Degradative Extraction Method for Molecular Structure Characterization of Bacterial Glycogen Particles.

Jun-Jiao Wang, Meng-Meng Wang, You-Wei He, Zhang-Wen Ma, Zi-Yi Wang, Rui Qiao, Xin-Le Tan, Qing-Hua Liu, Liang Wang.

Currently, there exist a variety of glycogen extraction methods, which either damage glycogen spatial structure or only partially extract glycogen, leading to the biased characterization of glycogen fine molecular structure. To understand the dynamic changes of glycogen structures and the versatile functions of glycogen particles in bacteria, it is essential to isolate glycogen with minimal degradation. In this study, a mild glycogen isolation method is demonstrated by using cold-water (CW) precipitation via sugar density gradient ultra-centrifugation (SDGU-CW). The traditional trichloroacetic acid (TCA) method and potassium hydroxide (KOH) method were also performed for comparison. A commonly used lab strain, Escherichia coli BL21(DE3), was used as a model organism in this study for demonstration purposes. After extracting glycogen particles using different methods, their structures were analyzed and compared through size exclusion chromatography (SEC) for particle size distribution and fluorophore-assisted capillary electrophoresis (FACE) for linear chain length distributions. The analysis confirmed that glycogen extracted via SDGU-CW had minimal degradation.

DOI: https://doi.org/10.3791/63016
BMJ Case Rep. 2022 Mar 09. pii: e247312. [Epub ahead of print]15(3):

Non-specificity of symptoms in infantile-onset Pompe disease may delay the diagnosis and institution of treatment.

Udara Dilrukshi Senarathne, Eresha Jasinge, Sarojini Viknarajah Mohan, Samantha Waidyanatha.

  Pompe disease is an autosomal-recessive inherited disorder of glycogen metabolism due to lysosomal acid alpha-glucosidase deficiency. The infantile-onset form is rapidly fatal if left untreated and presents with respiratory symptoms, a typical encounter during infancy. We discuss two infants presenting with respiratory symptoms since early infancy and found to have cardiomegaly, hypotonia, elevated muscle enzymes, leading to the diagnosis of Pompe disease with genetic confirmation. However, both infants expired before the enzyme replacement therapy due to complications of irreversible muscle damage despite supportive medical care. Presentation with respiratory symptoms common during childhood, absence of alarming symptoms such as hypoglycaemia, ketoacidosis or encephalopathy, and relative rarity of Pompe disease can contribute to lapses in the early diagnosis as observed in the index patients. Thus, these cases emphasise the importance of vigilant assessment of common paediatric presentations, which may be presenting symptoms of underlying sinister pathologies.

Keywords:  congenital disorders; genetic screening / counselling; pathology

DOI:  https://doi.org/10.1136/bcr-2021-247312
Mini Rev Med Chem. 2022 Mar 09.

The Role of IL-6 Released During Exercise to Insulin Sensitivity and Muscle Hypertrophy.

Álvaro Nóbrega de Melo Madureira, João Ricardhis Saturnino de Oliveira, Vera Lúcia de Menezes Lima.

  Interleukin-6 (IL-6) influences both inflammatory response and anti-inflammatory processes. This cytokine can be released by the exercising skeletal muscle, which characterizes it as a myokine. Unlike what is observed in inflammation, IL-6 produced by skeletal muscle is not preceded by the release of other pro-inflammatory cytokines, but is seems to be dependent on the lactate produced during exercise, thus causing different effects from those of seen in inflammatory state. After binding to its receptor, myokine IL-6 activates the PI3K-Akt pathway. One consequence of this upregulation is the potentiation of insulin signaling, which enhances insulin sensitivity. IL-6 increases GLUT-4 vesicle mobilization to muscle cell periphery, increasing the glucose transport into the cell, and also glycogen synthesis. Muscle glycogen provides energy for the ATP resynthesis, and regulates Ca2+ release by the sarcoplasmic reticulum, influencing muscle contraction, and, hence, muscle function by multiple pathways. Another implication for the upregulation of PI3K-Akt pathway is the activation of mTORC1, which regulates mRNA translational efficiency by regulating translation machinery, and translational capacity by inducing ribosomal biogenesis. Thus, IL-6 may contribute for skeletal muscle hypertrophy and function by increasing contractile protein synthesis.

Keywords:  Cytokine; TNF-α; diabetes; glucose; glycogen.; hypertrophy

DOI:  https://doi.org/10.2174/1389557522666220309161245
Nutrients. 2022 Feb 27. pii: 1011. [Epub ahead of print]14(5):

Anti-Fatigue and Exercise Performance Improvement Effect of Glossogyne tenuifolia Extract in Mice.

Yi-Ju Chen, Rathinasamy Baskaran, Marthandam Asokan Shibu, Wan-Teng Lin.

  Glossogyne tenuifolia (GT) is a native perennial plant growing across the coastline areas in Taiwan. The current study aimed to examine the efficacy of GT extract in ameliorating physical fatigue during exercise and increasing exercise performance. Fifty male Institute of Cancer Research (ICR) mice were randomly segregated into five groups (n = 10) to GT extract orally for 4 weeks, at different concentrations (50, 100, 250, and 500 mg/kg BW/day): LGT 1X, MGT 2X, HGT 5X, and HGT 10X groups. Forelimb grip strength, endurance swimming time, serum biochemical marker levels, blood lipid profile and histological analysis of various organs were performed to assess the anti-fatigue effect and exercise performance of GT extract. The forelimb-grips strength and endurance-swimming time of GT-administered mice were increased significantly in a dose-dependent manner when compared to the control. Serum glucose, creatine kinase, and lactate levels were increased significantly in the HGT 10X group. Liver marker serum glutamic-oxaloacetic transaminase (GOT) was increased in the HGT 5X and HGT 10X groups, whereas Serum Glutamic Pyruvic Transaminase (GPT) was not altered. Renal markers, creatinine and uric acid levels, were not altered. Muscle and hepatic glycogen levels, which are essential for energy sources during exercise, were also significantly increased in a dose-dependent manner in all GT extract groups. No visible histological aberrations were observed in the vital organs after GT extract administration. The supplementation with GT extract could have beneficial effects on exercise performance and anti-fatigue function without toxicity at a higher dose.

Keywords:  Glossogyne tenuifolia; ammonia; creatine kinase; exercise; forelimb grip strength; lactate

DOI:  https://doi.org/10.3390/nu14051011
J Exp Biol. 2022 Mar 08. pii: jeb243380. [Epub ahead of print]225(Suppl_1):

Scaling of fibre area and fibre glycogen concentration in the hindlimb musculature of monitor lizards: implications for locomotor performance with increasing body size.

Robert L Cieri, Taylor J M Dick, Jeremy S Morris, Christofer J Clemente.

  A considerable biomechanical challenge faces larger terrestrial animals as the demands of body support scale with body mass (Mb), while muscle force capacity is proportional to muscle cross-sectional area, which scales with Mb2/3. How muscles adjust to this challenge might be best understood by examining varanids, which vary by five orders of magnitude in size without substantial changes in posture or body proportions. Muscle mass, fascicle length and physiological cross-sectional area all scale with positive allometry, but it remains unclear, however, how muscles become larger in this clade. Do larger varanids have more muscle fibres, or does individual fibre cross-sectional area (fCSA) increase? It is also unknown if larger animals compensate by increasing the proportion of fast-twitch (higher glycogen concentration) fibres, which can produce higher force per unit area than slow-twitch fibres. We investigated muscle fibre area and glycogen concentration in hindlimb muscles from varanids ranging from 105 g to 40,000 g. We found that fCSA increased with modest positive scaling against body mass (Mb0.197) among all our samples, and ∝Mb0.278 among a subset of our data consisting of never-frozen samples only. The proportion of low-glycogen fibres decreased significantly in some muscles but not others. We compared our results with the scaling of fCSA in different groups. Considering species means, fCSA scaled more steeply in invertebrates (∝Mb0.575), fish (∝Mb0.347) and other reptiles (∝Mb0.308) compared with varanids (∝Mb0.267), which had a slightly higher scaling exponent than birds (∝Mb0.134) and mammals (∝Mb0.122). This suggests that, while fCSA generally increases with body size, the extent of this scaling is taxon specific, and may relate to broad differences in locomotor function, metabolism and habitat between different clades.

Keywords:  Fibre type; Muscle architecture; Musculoskeletal system; Reptiles; Scaling; Varanids

DOI:  https://doi.org/10.1242/jeb.243380
J Sports Sci. 2022 Mar 06. 1-20

Physical loading in professional soccer players: Implications for contemporary guidelines to encompass carbohydrate periodization.

Liam Anderson, Barry Drust, Graeme L Close, James P Morton.

  Despite more than four decades of research examining the physical demands of match-play, quantification of the customary training loads of adult male professional soccer players is comparatively recent. The training loads experienced by players during weekly micro-cycles are influenced by phase of season, player position, frequency of games, player starting status, player-specific training goals and club coaching philosophy. From a macronutrient perspective, the periodization of physical loading within (i.e., match versus training days) and between contrasting micro-cycles (e.g., 1, 2 or 3 games per week schedules) has implications for daily carbohydrate (CHO) requirements. Indeed, aside from the well-recognised role of muscle glycogen as the predominant energy source during match-play, it is now recognised that the glycogen granule may exert regulatory roles in activating or attenuating the molecular machinery that modulate skeletal muscle adaptations to training. With this in mind, the concept of CHO periodization is gaining in popularity, whereby CHO intake is adjusted day-by-day and meal-by-meal according to the fuelling demands and specific goals of the upcoming session. On this basis, the present paper provides a contemporary overview and theoretical framework for which to periodize CHO availability for the professional soccer player according to the "fuel for the work" paradigm.

Keywords:  Glycogen; football; skeletal muscle; soccer; training adaptation

DOI:  https://doi.org/10.1080/02640414.2022.2044135
Nutrients. 2022 Jan 18. pii: 404. [Epub ahead of print]14(3):

d-Allulose Improves Endurance and Recovery from Exhaustion in Male C57BL/6J Mice.

Bingyang Liu, Yang Gou, Takamasa Tsuzuki, Takako Yamada, Tetsuo Iida, Sixian Wang, Ryoichi Banno, Yukiyasu Toyoda, Teruhiko Koike.

  d-Allulose, a rare sugar, improves glucose metabolism and has been proposed as a candidate calorie restriction mimetic. This study aimed to investigate the effects of d-allulose on aerobic performance and recovery from exhaustion and compared them with the effects of exercise training. Male C57BL/6J mice were subjected to exercise and allowed to run freely on a wheel. Aerobic performance was evaluated using a treadmill. Glucose metabolism was analyzed by an intraperitoneal glucose tolerance test (ipGTT). Skeletal muscle intracellular signaling was analyzed by Western blotting. Four weeks of daily oral administration of 3% d-allulose increased running distance and shortened recovery time as assessed by an endurance test. d-Allulose administration also increased the maximal aerobic speed (MAS), which was observed following treatment for >3 or 7 days. The improved performance was associated with lower blood lactate levels and increased liver glycogen levels. Although d-allulose did not change the overall glucose levels as determined by ipGTT, it decreased plasma insulin levels, indicating enhanced insulin sensitivity. Finally, d-allulose enhanced the phosphorylation of AMP-activated protein kinase and acetyl-CoA carboxylase and the expression of peroxisome proliferator-activated receptor γ coactivator 1α. Our results indicate that d-allulose administration enhances endurance ability, reduces fatigue, and improves insulin sensitivity similarly to exercise training. d-Allulose administration may be a potential treatment option to alleviate obesity and enhance aerobic exercise performance.

Keywords:  aerobic performance; blood lactate; d-allulose; glycogen; maximal aerobic speed; recovery; skeletal muscle

DOI:  https://doi.org/10.3390/nu14030404
EMBO J. 2022 Mar 11. e109700

HOIL-1 ubiquitin ligase activity targets unbranched glucosaccharides and is required to prevent polyglucosan accumulation.

Ian R Kelsall, Elisha H McCrory, Yingqi Xu, Cheryl L Scudamore, Sambit K Nanda, Paula Mancebo-Gamella, Nicola T Wood, Axel Knebel, Stephen J Matthews, Philip Cohen.

  HOIL-1, a component of the linear ubiquitin chain assembly complex (LUBAC), ubiquitylates serine and threonine residues in proteins by esterification. Here, we report that mice expressing an E3 ligase-inactive HOIL-1[C458S] mutant accumulate polyglucosan in brain, heart and other organs, indicating that HOIL-1's E3 ligase activity is essential to prevent these toxic polysaccharide deposits from accumulating. We found that HOIL-1 monoubiquitylates glycogen and α1:4-linked maltoheptaose in vitro and identify the C6 hydroxyl moiety of glucose as the site of ester-linked ubiquitylation. The monoubiquitylation of maltoheptaose was accelerated > 100-fold by the interaction of Met1-linked or Lys63-linked ubiquitin oligomers with the RBR domain of HOIL-1. HOIL-1 also transferred pre-formed ubiquitin oligomers to maltoheptaose en bloc, producing polyubiquitylated maltoheptaose in one catalytic step. The Sharpin and HOIP components of LUBAC, but not HOIL-1, bound to unbranched and infrequently branched glucose polymers in vitro, but not to highly branched mammalian glycogen, suggesting a potential function in targeting HOIL-1 to unbranched glucosaccharides in cells. We suggest that monoubiquitylation of unbranched glucosaccharides may initiate their removal from cells, preventing precipitation as polyglucosan.

Keywords:  RBCK1; RBR E3 ligase; glycogen; polyglucosan; ubiquitination

DOI:  https://doi.org/10.15252/embj.2021109700
Int J Biol Macromol. 2022 Mar 02. pii: S0141-8130(22)00454-8. [Epub ahead of print]206 567-579

Role of polyphenols in combating Type 2 Diabetes and insulin resistance.

Moyad Shahwan, Fahad Alhumaydhi, Ghulam Md Ashraf, Prince M Z Hasan, Anas Shamsi.

  Compromised carbohydrate metabolism leading to hyperglycemia is the primary metabolic disorder of non-insulin-dependent diabetes mellitus. Reformed digestion and altered absorption of carbohydrates, exhaustion of glycogen stock, enhanced gluconeogenesis and overproduced hepatic glucose, dysfunction of β-cell, resistance to insulin in peripheral tissue, and impaired insulin signaling pathways are essential reasons for hyperglycemia. Although oral anti-diabetic drugs like α-glucosidase inhibitors, sulfonylureas and insulin therapies are commonly used to manage Type 2 Diabetes (T2D) and hyperglycemia, natural compounds in diet also play a significant role in combating the effect of diabetes. Due to their vast bioavailability and anti-hyperglycemic effect with least or no side effects, polyphenolic compounds have gained wide popularity. Polyphenols such as flavonoids and tannins play a significant role in carbohydrate metabolism by inhibiting key enzymes responsible for the digestion of carbohydrates to glucose, viz. α-glucosidase and α-amylase. Several polyphenols such as resveratrol, epigallocatechin-3-gallate (EGCG) and quercetin enhanced glucose uptake in the muscles and adipocytes by translocating GLUT4 to plasma membrane mainly by the activation of the AMP-activated protein kinase (AMPK) pathway. This review provides an insight into the protective role of polyphenols in T2D, highlighting the aspects of insulin resistance.

Keywords:  Insulin resistance; Polyphenols; Type 2 diabetes

DOI:  https://doi.org/10.1016/j.ijbiomac.2022.03.004
Cell Regen. 2022 Mar 07. 11(1): 8

Linc-RAM promotes muscle cell differentiation via regulating glycogen phosphorylase activity.

Lili Zhai, Xin Wan, Rimao Wu, Xiaohua Yu, Hu Li, Ran Zhong, Dahai Zhu, Yong Zhang.

  Long non-coding RNAs (lncRNAs) are important regulators of diverse biological processes, especially skeletal muscle cell differentiation. Most of the lncRNAs identified to date are localized in the nucleus and play regulatory roles in gene expression. The cytoplasmic lncRNAs are less well understood. We previously identified a long intergenic non-coding RNA (linc-RNA) activator of myogenesis (Linc-RAM) that directly binds MyoD in the nucleus to enhance muscle cell differentiation. Here, we report that a substantial fraction of Linc-RAM is localized in the cytoplasm of muscle cells. To explore the molecular functions of cytoplasmic Linc-RAM, we sought to identify Linc-RAM-binding proteins. We report here that Linc-RAM physically interacts with glycogen phosphorylase (PYGM) in the cytoplasm. Knockdown of PYGM significantly attenuates the function of Linc-RAM in promoting muscle cell differentiation. Loss-of-function and gain-of function assays demonstrated that PYGM enhances muscle cell differentiation in an enzymatic activity-dependent manner. Finally, we show that the interaction between Linc-RAM and PYGM positively regulates the enzymatic activity of PYGM in muscle cells. Collectively, our findings unveil a molecular mechanism through which cytoplasmic Linc-RAM contributes to muscle cell differentiation by regulating PYGM activity. Our findings establish that there is crosstalk between lncRNAs and cellular metabolism during myogenic cell differentiation.

Keywords:  Cytoplasm; Glycogen phosphorylase; Linc-RAM; Long non-coding RNAs; Muscle cell differentiation

DOI:  https://doi.org/10.1186/s13619-022-00109-8
Int J Mol Sci. 2022 Feb 22. pii: 2408. [Epub ahead of print]23(5):

Nanoparticle Delivery Platforms for RNAi Therapeutics Targeting COVID-19 Disease in the Respiratory Tract.

Yuan Zhang, Juhura G Almazi, Hui Xin Ong, Matt D Johansen, Scott Ledger, Daniela Traini, Philip M Hansbro, Anthony D Kelleher, Chantelle L Ahlenstiel.

  Since December 2019, a pandemic of COVID-19 disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread across the globe. At present, the Food and Drug Administration (FDA) has issued emergency approval for the use of some antiviral drugs. However, these drugs still have limitations in the specific treatment of COVID-19, and as such, new treatment strategies urgently need to be developed. RNA-interference-based gene therapy provides a tractable target for antiviral treatment. Ensuring cell-specific targeted delivery is important to the success of gene therapy. The use of nanoparticles (NPs) as carriers for the delivery of small interfering RNA (siRNAs) to specific tissues or organs of the human body could play a crucial role in the specific therapy of severe respiratory infections, such as COVID-19. In this review, we describe a variety of novel nanocarriers, such as lipid NPs, star polymer NPs, and glycogen NPs, and summarize the pre-clinical/clinical progress of these nanoparticle platforms in siRNA delivery. We also discuss the application of various NP-capsulated siRNA as therapeutics for SARS-CoV-2 infection, the challenges with targeting these therapeutics to local delivery in the lung, and various inhalation devices used for therapeutic administration. We also discuss currently available animal models that are used for preclinical assessment of RNA-interference-based gene therapy. Advances in this field have the potential for antiviral treatments of COVID-19 disease and could be adapted to treat a range of respiratory diseases.

Keywords:  COVID-19; glycogen nanoparticles; inhalation; lipid nanoparticles; nanomedicine; nanoparticle-capsulated drug delivery; polymer nanoparticles; siRNA

DOI:  https://doi.org/10.3390/ijms23052408
Front Sports Act Living. 2022 ;4 852230

New Opportunities to Advance the Field of Sports Nutrition.

Kristin L Jonvik, Michelle King, Ian Rollo, Trent Stellingwerff, Yannis Pitsiladis.

  Sports nutrition is a relatively new discipline; with ~100 published papers/year in the 1990s to ~3,500+ papers/year today. Historically, sports nutrition research was primarily initiated by university-based exercise physiologists who developed new methodologies that could be impacted by nutrition interventions (e.g., carbohydrate/fat oxidation by whole body calorimetry and muscle glycogen by muscle biopsies). Application of these methods in seminal studies helped develop current sports nutrition guidelines as compiled in several expert consensus statements. Despite this wealth of knowledge, a limitation of the current evidence is the lack of appropriate intervention studies (e.g., randomized controlled clinical trials) in elite athlete populations that are ecologically valid (e.g., in real-life training and competition settings). Over the last decade, there has been an explosion of sports science technologies, methodologies, and innovations. Some of these recent advances are field-based, thus, providing the opportunity to accelerate the application of ecologically valid personalized sports nutrition interventions. Conversely, the acceleration of novel technologies and commercial solutions, especially in the field of biotechnology and software/app development, has far outstripped the scientific communities' ability to validate the effectiveness and utility of the vast majority of these new commercial technologies. This mini-review will highlight historical and present innovations with particular focus on technological innovations in sports nutrition that are expected to advance the field into the future. Indeed, the development and sharing of more "big data," integrating field-based measurements, resulting in more ecologically valid evidence for efficacy and personalized prescriptions, are all future key opportunities to further advance the field of sports nutrition.

Keywords:  athletes; diet; health; innovation; performance; technology; wearables; wellness

DOI:  https://doi.org/10.3389/fspor.2022.852230
Front Cell Dev Biol. 2022 ;10 793566

Bioimpedance Phase Angle as a Prognostic Tool in Late-Onset Pompe Disease: A Single-Centre Prospective Study With a 15-year Follow-Up.

Sabrina Ravaglia, Rachele de Giuseppe, Annalisa Carlucci, Susan Jehne, Grazia Crescimanno, Lara Ahmad, Matteo Paoletti, Gabriele Clemente, Anna Pichiecchio, Rosella Bazzano, Serena Cirio, Enza Maria Valente, Cesare Danesino, Paola De Filippi, Alice Tartara, Hellas Cena.

  Background: Late-onset Pompe disease (LOPD) is an autosomal-recessive metabolic myopathy caused by deficiency of the lysosomal enzyme Acid Alpha-Glucosidase (GAA), leading to glycogen accumulation in proximal and axial muscles, and in the diaphragm. Enzyme Replacement Therapy (ERT) with recombinant GAA became available in 2006. Since then, several outcome measures have been investigated for the adequate follow-up of disease progression and treatment response, usually focusing on respiratory and motor function. Prognostic factors predicting outcome have not been identified till now. Methods: In this single Centre, prospective study, we evaluate the response to enzyme replacement therapy in 15 patients (7 males) with LOPD in different stages of disease, aged 49.4 ± 16.1, followed-up for 15 years. Treatment response was measured by the 6-min walking test, vital capacity in supine and upright position, respiratory muscle strength, muscle MRI, manual muscle testing. We investigated the usefulness of Body Impedance Vectorial Analysis for serial body composition assessment. Results: Although most patients with LOPD benefit from long-term treatment, some secondary decline may occur after the first 3-5 years. Some nutritional (lower body mass index, higher fat free mass, higher phase angle) and disease parameters (higher creatinine and shorter disease duration at the beginning of treatment) seem to predict a better motor outcome. Lower Phase Angle, possibly reflecting loss of integrity of skeletal muscle membranes and thus treatment mis-targeting, seems to correlate with worse treatment response on long-term follow-up. Conclusion: Body Impedance Vectorial Analysis is a fast, easily performed and cheap tool that may be able to predict long-term treatment response in patients with LOPD. Low Phase angle may serve as a marker of muscle quality and may be used to predict the response to a muscle-targeted intervention such as ERT, thus improving the identification of patients needing a closer follow-up due to higher fragility and risk of deterioration.

Keywords:  enzyme replacement therapy; late-onset pompe disease; long-term effectiveness; nutritional assessment; outcome

DOI:  https://doi.org/10.3389/fcell.2022.793566
J Food Sci. 2022 Mar 11.

Hypoglycemic and hypolipidemic effects of polysaccharide isolated from Sphacelotheca sorghi in diet-streptozotocin-induced T2D mice.

Xin Fu, Mengxue Song, Ming Lu, Mengxi Xie, Lin Shi.

  Edible fungus has attracted great interest with many health benefits, and polysaccharides from them have shown great potentials. In this study, polysaccharides were extracted from Sphacelotheca sorghi (Link) Clint. Monosaccharide composition of S. sorghi polysaccharides (SSP) was detected by high-performance anion exchange chromatography (HPAEC) and mainly consists of glucose (70.5%), galactose (15.6%), mannose (7.2%), arabinose (5.8%), and rhamnose (0.9%). Type 2 diabetes (T2D) was induced by a high-fat, high-sugar diet-fed (HFSD) diet with streptozotocin (STZ) injection in mice, and hypoglycemic and hypolipidemic regulations of SSP were evaluated. After oral treatment of high dose of SSP (200 mg/kg/day), the fasting blood glucose (FBG) was reduced by 39.3%, the insulin resistance of T2D mice was relieved, the lipids metabolism disorder caused by diabetes was improved, and the levels of liver glycogen was increased by 34.1%, compared with the model control. Histopathological examination showed that SSP relieved liver damage. Furthermore, SSP regulated glucose and lipid metabolism by activating phosphoinositide 3-kinase/Akt signaling pathway. Overall, SPP is promising to be used as a functional food for the improvement of metabolic disorders. PRACTICAL APPLICATION: For enhancing the utilization rate and economic value of an edible fungi Sphacelotheca sorghi (Link) Clint., the total polysaccharides were isolated and used to investigate the effect of fungi in terms of balancing the levels of blood glucose and lipids. The S. sorghi polysaccharide treatment resolved the symptoms and insulin resistance in mice with diabetes, signifying its potential application in producing different functional foods for preventing or controlling diabetes.

Keywords:  PI3K/Akt signaling pathway; Sphacelotheca sorghi (Link) Clint polysaccharide; insulin resistance; type 2 diabetes

DOI:  https://doi.org/10.1111/1750-3841.16091
PLoS One. 2022 ;17(3): e0264347

Characterisation of breast cancer molecular signature and treatment assessment with vibrational spectroscopy and chemometric approach.

Magdalena Kołodziej, Ewa Kaznowska, Sylwia Paszek, Józef Cebulski, Edyta Barnaś, Marian Cholewa, Jitraporn Vongsvivut, Izabela Zawlik.

Triple negative breast cancer (TNBC) is regarded as the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies, resulting in many patients with recurrent. The insight into the detailed biochemical composition of TNBC would help develop dedicated treatments. Thus, in this study Fourier Transform Infrared microspectroscopy combined with chemometrics and absorbance ratios investigation was employed to compare healthy controls with TNBC tissue before and after chemotherapy within the same patient. The primary spectral differences between control and cancer tissues were found in proteins, polysaccharides, and nucleic acids. Amide I/Amide II ratio decrease before and increase after chemotherapy, whereas DNA, RNA, and glycogen contents increase before and decrease after the treatment. The chemometric results revealed discriminatory features reflecting a clinical response scheme and proved the chemotherapy efficacy assessment with infrared spectroscopy is possible.

DOI: https://doi.org/10.1371/journal.pone.0264347
Sci Rep. 2022 Mar 10. 12(1): 3945

miR-378 affects metabolic disturbances in the mdx model of Duchenne muscular dystrophy.

Paulina Podkalicka, Olga Mucha, Katarzyna Kaziród, Krzysztof Szade, Jacek Stępniewski, Liudmyla Ivanishchuk, Hirofumi Hirao, Ewelina Pośpiech, Alicja Józkowicz, Jerzy W Kupiec-Weglinski, Józef Dulak, Agnieszka Łoboda.

Although Duchenne muscular dystrophy (DMD) primarily affects muscle tissues, the alterations to systemic metabolism manifested in DMD patients contribute to the severe phenotype of this fatal disorder. We propose that microRNA-378a (miR-378) alters carbohydrate and lipid metabolism in dystrophic mdx mice. In our study, we utilized double knockout animals which lacked both dystrophin and miR-378 (mdx/miR-378-/-). RNA sequencing of the liver identified 561 and 194 differentially expressed genes that distinguished mdx versus wild-type (WT) and mdx/miR-378-/- versus mdx counterparts, respectively. Bioinformatics analysis predicted, among others, carbohydrate metabolism disorder in dystrophic mice, as functionally proven by impaired glucose tolerance and insulin sensitivity. The lack of miR-378 in mdx animals mitigated those effects with a faster glucose clearance in a glucose tolerance test (GTT) and normalization of liver glycogen levels. The absence of miR-378 also restored the expression of genes regulating lipid homeostasis, such as Acly, Fasn, Gpam, Pnpla3, and Scd1. In conclusion, we report for the first time that miR-378 loss results in increased systemic metabolism of mdx mice. Together with our previous finding, demonstrating alleviation of the muscle-related symptoms of DMD, we propose that the inhibition of miR-378 may represent a new strategy to attenuate the multifaceted symptoms of DMD.

DOI: https://doi.org/10.1038/s41598-022-07868-z
J Invertebr Pathol. 2022 Mar 03. pii: S0022-2011(22)00024-6. [Epub ahead of print]190 107739

High prevalence of CsRV2 in cultured Callinectes danae: Potential impacts on soft-shell crab production in Brazil.

Camila Prestes Dos Santos Tavares, Mingli Zhao, Éverton Lopes Vogt, Jorge Felipe Argenta Model, Anapaula Sommer Vinagre, Ubiratan de Assis Teixeira da Silva, Antonio Ostrensky, Eric James Schott.

  Crabs can be infected by a variety of pathogenic micro-organisms but the most damaging are viruses. Naturally-occurring Callinectes sapidus reovirus 1 (CsRV1) is thought to contribute to mortality of Callinectes sapidus in soft crab culture in the USA. In Brazil, soft crabs are frequently produced using Callinectes danae, which suffers a similar rate of mortality in culture as C. sapidus. This study investigated whether CsRV1 could be detected in healthy or dead Callinectes danae from Paraná, Brazil and kept in captivity, we also evaluated the relationship between viral infection, and biochemical and behavioral parameters. C. danae from Paranaguá Bay were kept in a recirculation system for 14 days and subjected to weekly biochemical analyses and a reflex action mortality predictors (RAMP) test. RT-qPCR assays for CsRV1 were negative for all samples. However, electrophoretic analysis of extracted RNA from some crabs showed a pattern of 12 dsRNA bands that indicated intense infection by a reovirus with a genome organization different from CsRV1. The banding pattern was indistinguishable from a putative novel reovirus detected in C. sapidus in Rio Grande do Sul, Brazil, provisionally called CsRV2. The prevalence of dsRNA of CsRV2 showed no significant difference between crabs that died and survived. Interestingly, the presence of CsRV2 dsRNA was correlated with a significant reduction in glycogen concentration in hepatopancreas and a decrease in reflex action. The results obtained in this study are an early glimpse of the occurrence of reoviruses in C. danae and their potential effects in soft-shell crab systems in Brazil.

Keywords:  Blue crab; CsRV2; Glycogen; RAMP; Reovirus; Total proteins

DOI:  https://doi.org/10.1016/j.jip.2022.107739