Role of Glucocorticoid Signaling and HDAC4 Activation in Diaphragm and Gastrocnemius Proteolytic Activity in Septic Rats.

Sepsis increases glucocorticoid and decreases IGF-1, leading to skeletal muscle wasting and cachexia. Muscle atrophy mainly takes place in locomotor muscles rather than in respiratory ones. Our study aimed to elucidate the mechanism responsible for this difference in muscle proteolysis, focusing on local inflammation and IGF-1 as well as on their glucocorticoid response and HDAC4-myogenin activation. Sepsis was induced in adult male rats by lipopolysaccharide (LPS) injection (10 mg/kg), and 24 h afterwards, rats were euthanized. LPS increased TNFα and IL-10 expression in both muscles studied, the diaphragm and gastrocnemius, whereas IL-6 and SOCS3 mRNA increased only in diaphragm. In comparison with gastrocnemius, diaphragm showed a lower increase in proteolytic marker expression (atrogin-1 and LC3b) and in LC3b protein lipidation after LPS administration. LPS increased the expression of glucocorticoid induced factors, KLF15 and REDD1, and decreased that of IGF-1 in gastrocnemius but not in the diaphragm. In addition, an increase in HDAC4 and myogenin expression was induced by LPS in gastrocnemius, but not in the diaphragm. In conclusion, the lower activation of both glucocorticoid signaling and HDAC4-myogenin pathways by sepsis can be one of the causes of lower sepsis-induced proteolysis in the diaphragm compared to gastrocnemius.Fac. de Enfermería, Fisioterapia y PodologíaTRUESpanish Ministry of Economy and CompetitivenessFondo Europeo de Desarrollo Regional (FEDER)European CommissionComunidad de MadridFundación SenefroFundación Mutua Madrileñapu

Olive Leaf Extract Supplementation to Old Wistar Rats Attenuates Aging-Induced Sarcopenia and Increases Insulin Sensitivity in Adipose Tissue and Skeletal Muscle

Aging is associated with increased visceral adiposity and a decrease in the amount of brown adipose tissue and muscle mass, known as sarcopenia, which results in the development of metabolic alterations such as insulin resistance. In this study, we aimed to analyze whether 3-week supplementation with a phenolic-rich olive leaf extract (OLE) to 24 months-old male Wistar rats orally (100 mg/kg) attenuated the aging-induced alterations in body composition and insulin resistance. OLE treatment increased brown adipose tissue and attenuated the aging-induced decrease in protein content and gastrocnemius weight. Treatment with OLE prevented the aging-induced increase in the expression of PPAR-γ in visceral and brown adipose tissues, while it significantly increased the expression of PPAR-α in the gastrocnemius of old rats and reduced various markers related to sarcopenia such as myostatin, HDAC-4, myogenin and MyoD. OLE supplementation increased insulin sensitivity in explants of gastrocnemius and epididymal visceral adipose tissue from aged rats through a greater activation of the PI3K/Akt pathway, probably through the attenuation of inflammation in both tissues. In conclusion, supplementation with OLE prevents the loss of muscle mass associated with aging and exerts anti-inflammatory and insulin-sensitizing effects on adipose tissue and skeletal muscle

Addition of Olive Leaf Extract to a Mixture of Algae and Extra Virgin Olive Oils Decreases Fatty Acid Oxidation and Synergically Attenuates Age-Induced Hypertension, Sarcopenia and Insulin Resistance in Rats

Olive-derived products, such as virgin olive oil (EVOO) and/or olive leaf extracts (OLE), exert anti-inflammatory, insulin-sensitizing and antihypertensive properties and may be useful for stabilizing omega 3 fatty acids (n-3 PUFA) due to their high content in antioxidant compounds. In this study, the addition of OLE 4:0.15 (w/w) to a mixture of algae oil (AO) rich in n-3 PUFA and EVOO (25:75, w/w) prevents peroxides formation after 12 months of storage at 30 °C. Furthermore, the treatment with the oil mixture (2.5 mL/Kg) and OLE (100 mg/Kg) to 24 month old Wistar rats for 21 days improved the lipid profile, increased the HOMA-IR and decreased the serum levels of miRNAs 21 and 146a. Treatment with this new nutraceutical also prevented age-induced insulin resistance in the liver, gastrocnemius and visceral adipose tissue by decreasing the mRNA levels of inflammatory and oxidative stress markers. Oil mixture + OLE also attenuated the age-induced alterations in vascular function and prevented muscle loss by decreasing the expression of sarcopenia-related markers. In conclusion, treatment with a new nutraceutical based on a mixture of EVOO, AO and OLE is a useful strategy for improving the stability of n-3 PUFA in the final product and to attenuate the cardiometabolic and muscular disorders associated with aging

Aprendizaje cooperativo con “SAve Me, please”

Los objetivos de este trabajo fueron: (1) mejorar los hábitos de estudio y el aprendizaje fomentando el trabajo continuo y, (2) acercar la metodología del trabajo cooperativo a los estudiantes. Para ello, se desarrolló la herramienta de gamificación “SAve Me, please” que consiste en superar una serie de actividades en equipos para “salvar” a un paciente virtual denominado SAM. Esta herramienta se empleó en tres grupos docentes de la asignatura Fisiología Humana del Grado de Enfermería de la Universidad Complutense de Madrid. Tras su aplicación, se detectaron mejoras en las calificaciones de los estudiantes respecto al curso previo en el que no se empleó esta metodología. Además, los estudiantes expresaron su satisfacción con la metodología a través de una encuesta semicuantitativa anónima. De este modo, manifestaron mejoras en la valoración subjetiva de su aprendizaje, motivación e integración con los compañeros y los profesores, así como en su opinión sobre la calidad de la enseñanza recibida. Sus comentarios contribuyeron a proponer mejoras para optimizar las actividades y el funcionamiento de los equipos de trabajo. Por tanto, recomendamos ésta metodología para dinamizar asignaturas de Ciencias de la Salud, aunque también podría adaptarse a otras áreas de conocimiento

Uso de Twitter y la gamificación para fomentar el análisis crítico del conocimiento científico y las vías para su comunicación en estudiantes del Grado de Medicina

El objetivo del proyecto de innovación docente que se presenta fue mejorar la capacidad de análisis crítico del conocimiento científico en el alumnado del Grado de Medicina a través del uso de Twitter. Los estudiantes de la asignatura de Fisiología Humana compartieron a través de Twitter noticias científicas relacionadas con la asignatura. Tras una selección previa, el profesorado publicó un periódico online y los alumnos presentaron una de las noticias publicadas. Se realizó una encuesta online de evaluación del proyecto utilizando escalas de Likert (1-10). Los estudiantes respondieron que el proyecto había aumentado su capacidad de análisis crítico de la investigación biomédica (7,65; ds=1,71) y que la metodología había aumentado su interés por la asignatura (8,05; ds=1,69). La utilización de Twitter combinada con la exposición de noticias científicas resultó útil para mejorar la capacidad de análisis crítico de la evidencia científica biomédica, competencia básica del Grado de Medicina

Instagram y gamificación para incorporar los procesos fisiológicos al día a día de los estudiantes de Fisiología

El presente proyecto de innovación docente se basa en la utilización de la red social Instagram para incentivar el estudio diario y el aprendizaje cooperativo de una forma lúdica, autónoma y divertida. Se aplicó en la docencia de la Fisiología Humana en distintos grados en los que participa el Departamento de Fisiología. La metodología consiste en que los alumnos, trabajando en grupo, publiquen contenidos en Instagram, para repasar, sintetizar y compartir información de la asignatura. Los objetivos alcanzados fueron: motivación en el estudio continuado, implicación en el proceso de aprendizaje, trabajo en equipo y adquisición de competencias transversales como creatividad, liderazgo y compromiso. La participación en el proyecto fue muy alta (94%), así como la satisfacción de los alumnos, sobre todo en aspectos motivacionales (interés y curiosidad por la asignatura) y de integración, gracias al trabajo en equipo. En conclusión, la red Instagram es una herramienta útil como complemento de las clases, con objeto de incentivar el estudio diario, sintetizar la información y transmitirla mediante trabajo cooperativo

Formoterol treatment prevents the effects of endotoxin on muscle TNF/NF-kB, Akt/mTOR, and proteolytic pathways in a rat model. Role of IGF-I and miRNA 29b

Inflammatory diseases are associated with muscle wasting as a result of an increase in proteolysis. The purpose of this study was to elucidate whether administration of a β2 adrenergic agonist, formoterol, was able to prevent the acute effects of sepsis induced by liposaccharide (LPS) injection on rat gastrocnemius muscle and to evaluate the possible roles of corticosterone, IGF-I, miR-23a, and miR-29b. For this purpose, male Wistar rats were injected with LPS and/or formoterol. Formoterol treatment decreased LPS-induced increase in serum corticosterone, TNFα upregulation, and NF-κB(p65) and Forkhead box protein O1 activation in the gastrocnemius. Atrogin-1, muscle RING-finger protein-1, microtubule-associated protein-1 light chain 3b (LC3b), and the lipidation of LC3b-I to LC3b-II were increased by LPS, and formoterol blocked these effects. Serum IGF-I and its mRNA levels in the gastrocnemius were decreased, whereas mecano growth factor and IGF binding protein 3 mRNA levels were increased in the rats injected with LPS but not in the rats that received LPS and formoterol. Similarly, LPS decreased Akt and mammalian target of rapamycin phosphorylation, and formoterol blocked these decreases. Finally, miR-29b expression in the gastrocnemius was upregulated by endotoxin injection, whereas miR-23a was not significantly different. Formoterol treatment did not significantly modify LPS-induced increase in muscle miR-29b. Furthermore, in control rats formoterol increased the expression of this miRNA. We conclude that formoterol decreases endotoxin-induced inflammation and proteolysis in rat skeletal muscle. Those responses can be a direct effect of β2 adrenergic receptor stimulation or/and of blocking the effects of LPS on corticosterone and IGF-I. Muscle miR-23a and -29b do not seem to play an important role in those responses.Ministerio de Economía, Industria y CompetitividadDepto. de FisiologíaFac. de MedicinaTRUEpu

Melanocortin-4 receptor agonist (RO27-3225) ameliorates soleus but not gastrocnemius atrophy in arthritic rats

Adjuvant-induced arthritis in rats decreases body weight and muscle mass. Melanocyte stimulating hormone administration to arthritic rats decreases inflammation and skeletal muscle wasting. In this study, we investigate whether activation of melanocortin-4 receptor by RO27-3225 administration is able to prevent the effect of arthritis on the expression of muscle-specific E3 ubiquitin ligases and MyoD in two different muscles, gastrocnemius (a mainly fast type muscle) and soleus (slow type). Arthritis was induced in male Wistar rats by intradermal injection of Freund's adjuvant. Control and arthritic rats were injected with RO27-3225 (180 μg/kg i.p. twice a day) or saline, for 8 days. Body weight change, food intake and arthritis index were assessed daily. After sacrifice, serum insulin-like growth factor -1 (IGF-1) and corticosterone, as well as nuclear factor-κB(p65), cyclooxygenase-2 (COX-2), atrogene and MyoD in gastrocnemius and soleus were analysed. Administration of RO27-3225 to arthritic rats decreased arthritis scores, hind paw volume as well as nuclear factor-κB(p65) phosphorylation in gastrocnemius and soleus. However, RO27-3225 was not able to modify the effects of arthritis on serum IGF-1 and corticosterone. RO27-3225 ameliorates arthritis-induced decrease in food intake, body weight gain, epidydimal white adipose tissue and soleus weight, but not in gastrocnemius weight. Arthritis increased COX-2, atrogin-1 and MuRF1 expression in gastrocnemius and soleus, whereas RO27-3225 prevented this increase in soleus but not in gastrocnemius. Arthritis also increased MyoD expression in gastrocnemius and soleus (P < 0.01). RO27-3225 decreased MyoD expression in gastrocnemius but not in soleus of arthritic rats. In control rats RO27-3225 did not modify MyoD expression in gastrocnemius or soleus. In conclusion, our data suggest that in arthritic rats, RO27-3225 treatment decreases inflammation and muscle atrophy, preventing atrogene upregulation in slow type muscle but not in gastrocnemius. The lack of effect in the gastrocnemius can be related to the inability of RO27-3225 to prevent arthritis-induced corticosterone upregulation as well as IGF-1 downregulation.Depto. de FisiologíaFac. de MedicinaTRUEpu

Time-Dependent Changes in Muscle IGF1-IGFBP5-PAPP System after Sciatic Denervation

Denervation-induced muscle atrophy is a frequent cause of skeletal muscle diseases. However, the role of the most important muscle growth factor, insulin-like growth factor (IGF-1), in this process is poorly understood. IGF-1 activity is controlled by six IGF-1 binding proteins (IGFBPs). In skeletal muscle, IGFBP-5 seems to have an important role in atrophic processes. Furthermore, pappalysins (PAPP-A) modulate muscle growth by increasing IGF-1 bioavailability through IGFBP cleavage. We aimed to study the time-dependent changes in the IGF1-IGFBP5-PAPP system and its regulators in gastrocnemius muscle after sciatic denervation. Gastrocnemius atrophy and overexpression of IGF-1 was observed from day 3 post-denervation. The proteolytic factors measured were elevated from day 1 post-denervation onwards. Expression of both IGFBP-5 and pappalysins were increased on days 1 and 3. Subsequently, on days 7 to 14 pappalysins returned to control levels while IGFBP-5 remained elevated. The ratio IGFBP-5/PAPP-A was correlated with the main proteolytic markers. All data suggest that the initial increase of pappalysins could facilitate the IGF-1 action on muscle growth, whereas their subsequent decrease could lead to further muscle wasting.Unión EuropeaMinisterio de Economía y Competitividad-MINECOComunidad de MadridDepto. de FisiologíaFac. de MedicinaTRUEpu