Inhibition of Myostatin Signaling through Notch Activation following Acute Resistance Exercise

Myostatin is a TGFb family member and negative regulator of muscle size. Due to the complexity of the molecular pathway between myostatin mRNA/protein and changes in transcription, it has been difficult to understand whether myostatin plays a role in resistance exercise-induced skeletal muscle hypertrophy. To circumvent this problem, we determined the expression of a unique myostatin target gene, Mighty, following resistance exercise. Mighty mRNA increased by 6 h (82.9624.21%) and remained high out to 48 h (56.5619.67%) after resistance exercise. Further examination of the soleus, plantaris and tibialis anterior muscles showed that the change in Mighty mRNA at 6 h correlated with the increase in muscle size associated with this protocol (R2 = 0.9996). The increase in Mighty mRNA occurred both independent of Smad2 phosphorylation and in spite of an increase in myostatin mRNA (341.86147.14% at 3 h). The myostatin inhibitor SKI remained unchanged. However, activated Notch, another potential inhibitor of TGFb signaling, increased immediately following resistance exercise (83611.2%) and stayed elevated out to 6 h (78616.6%). Electroportion of the Notch intracellular domain into the tibialis anterior resulted in an increase in Mighty mRNA (63613.4%) that was equivalent to the canonical Notch target HES-1 (94.467.32%). These data suggest that acute resistance exercise decreases myostatin signaling through the activation of the TGFb inhibitor Notch resulting in a decrease in myostatin transcriptional activity that correlates well with muscle hypertrophy

Myostatin Inhibition in Muscle, but Not Adipose Tissue, Decreases Fat Mass and Improves Insulin Sensitivity

Myostatin (Mstn) is a secreted growth factor expressed in skeletal muscle and adipose tissue that negatively regulates skeletal muscle mass. Mstn−/− mice have a dramatic increase in muscle mass, reduction in fat mass, and resistance to diet-induced and genetic obesity. To determine how Mstn deletion causes reduced adiposity and resistance to obesity, we analyzed substrate utilization and insulin sensitivity in Mstn−/− mice fed a standard chow. Despite reduced lipid oxidation in skeletal muscle, Mstn−/− mice had no change in the rate of whole body lipid oxidation. In contrast, Mstn−/− mice had increased glucose utilization and insulin sensitivity as measured by indirect calorimetry, glucose and insulin tolerance tests, and hyperinsulinemic-euglycemic clamp. To determine whether these metabolic effects were due primarily to the loss of myostatin signaling in muscle or adipose tissue, we compared two transgenic mouse lines carrying a dominant negative activin IIB receptor expressed specifically in adipocytes or skeletal muscle. We found that inhibition of myostatin signaling in adipose tissue had no effect on body composition, weight gain, or glucose and insulin tolerance in mice fed a standard diet or a high-fat diet. In contrast, inhibition of myostatin signaling in skeletal muscle, like Mstn deletion, resulted in increased lean mass, decreased fat mass, improved glucose metabolism on standard and high-fat diets, and resistance to diet-induced obesity. Our results demonstrate that Mstn−/− mice have an increase in insulin sensitivity and glucose uptake, and that the reduction in adipose tissue mass in Mstn−/− mice is an indirect result of metabolic changes in skeletal muscle. These data suggest that increasing muscle mass by administration of myostatin antagonists may be a promising therapeutic target for treating patients with obesity or diabetes

A Comparative Study of Structural and Morphological Properties of Pristine and Mn Doped Ruthenium Oxide Thin Films.

Mn-doped and pristine Ruthenium Oxide composite nanostructures in thin film form were prepared on stainless steel substrates by sol-gel spin coating method. The at % of Mn was increased as 0.1, 0.2, 0.5, 1 and 2 %. The X-ray diffraction study showed crystalline behaviour for both pristine and doped films with porous morphology. The variation in lattice constants for both RuO2 and MnO2 was observed with increase in doping percentage. EDAX spectrum showed the successful doping of Mn in RuO2. The infrared spectrum of as deposited pristine RuO2 thin film depicted strong absorption bands at 880.41 cm-1 and 749.52 cm-1 indicating the stretching mode of Ru=O and O-Ru-O respectively. The absorption peaks attributed to the –OH bending vibrations along with Mn atoms were also seen

<span style="font-size:14.0pt;line-height: 115%;font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; color:black;mso-ansi-language:EN-IN;mso-fareast-language:EN-IN;mso-bidi-language: HI" lang="EN-IN">Chemically prepared Cd_1-xZn_xSe thin films: A correlation between compositional and structural analysis</span>

384-394<span style="font-size:14.0pt;line-height: 115%;font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:black;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN">The structural changes caused by the deliberate addition of Zn2+ into the lattice of CdSe have been investigated . Various Cd1-xZnxSe (0≤<span style="font-size:14.0pt;line-height:115%;font-family: " times="" new="" roman";mso-fareast-font-family:hiddenhorzocr;color:black;mso-ansi-language:="" en-in;mso-fareast-language:en-in;mso-bidi-language:hi"="" lang="EN-IN"> x ≤1) thin film structures were fabricated on the glass substrates at a deposition temperature of 70.2°C. The film composition was determined and compared with the bath composition. A non-linear relation has been observed between them. The XRD studies revealed a mixed structure (hexagonal and cubic) for CdSe whereas ZnSe films were cubic only. The structure of the Cd1-xZnxSe films is compositi on-dependent. It has been observed that Cd1-xZnxSe films are hexagonal wurtizite in structure for 0≤ x ≤0.2 wherein Zn2+ enters into the lattice of CdSe as a dopant. For 0.2≤ x ≤0.7  The films have been composed of the mixed phases of CdSe nncl ZnSe. It is interesting to note that CdSe and ZnSe form a solid solution for 0.7≤x≤1 which has indicated by the change in colour of the sample and shift in the peak position through d-increasing typically from 3.279 to 3.334Å. The lattice parameter (LP) varied continuously from 5.681 to 5.776Å for this range . Some reflections of SeO2, elemental Zn and  ZnO have also been detected for higher x-values.</span