Depletion of Branched-Chain Aminotransferase 2 (BCAT2) Enzyme Impairs Myoblast 3 Survival and Myotube Formation

Much is known about the positive effects of branched-chain amino acids (BCAA) in regulating muscle protein metabolism. Comparatively much less is known about the effects of these amino acids and their metabolites in regulating myotube formation. Using cultured myoblasts, we showed that although leucine is required for myotube formation, this requirement is easily met by α-ketoisocaproic acid, the ketoacid of leucine. We then demonstrated increases in the expression of the first two enzymes in the catabolism of the three BCAA, branched-chain amino transferase (BCAT2) and branched-chain α-ketoacid dehydrogenase (BCKD), with ~3× increase in BCKD protein expression (p < .05) during differentiation. Furthermore, depletion of BCAT2 abolished myoblast differentiation, as indicated by reduction in the levels of myosin heavy chain-1, troponin and myogenin. Supplementation of incubation medium with branched-chain α-ketoacids or related metabolites derivable from BCAT2 functions did not rescue the defects. However, co-depletion of BCKD kinase partially rescued the defects. Collectively, our data indicate a requirement for BCAA catabolism during myotube formation and that this requirement for BCAT2 likely goes beyond the need for this enzyme to generate the α-ketoacids of the BCAA.York University Librarie

Effect of Inflammation on Ketoisocaproic Acid Induced Insulin Resistance In Skeletal Muscle Cells

Branched-chain amino acids (BCAAs) have displayed metabolic benefits, and play a role in muscle protein synthesis. However, elevated levels of BCAAs and their metabolites have been linked to the pathogenesis of insulin resistance and type 2 diabetes mellitus. It has been demonstrated in my lab that -ketoisocaproic acid (KIC), a metabolite of leucine, inhibited insulin-stimulated glucose uptake, but is converted back to leucine in order to do so. Inflammation, a feature of insulin resistance may modulate the effects of amino acids and their metabolites on insulin action. Thus, I analyzed whether or not there was an additive effect of KIC and inflammation on insulin-stimulated glucose transport in L6 myotubes. Results emphasize previous findings, that even in the presence of inflammation, KIC is converted back to leucine to inhibit insulin-stimulated glucose uptake, suggesting that interventions altering BCAA pathway flux may help in the management/prevention of insulin resistance

Effects of Acute Muscle Contraction on the Key Molecules in Insulin and Akt Signaling in Skeletal Muscle in Health and in Insulin Resistant States

Insulin signaling plays a key role in glucose uptake, glycogen synthesis, and protein and lipid synthesis. In insulin-resistant states like obesity and type 2 diabetes mellitus, these processes are dysregulated. Regular physical exercise is a potential therapeutic strategy against insulin resistance, as an acute bout of exercise increases glucose disposal during the activity and for hours into recovery. Chronic exercise increases the activation of proteins involved in insulin signaling and increases glucose transport, even in insulin resistant states. Here, we will focus on the effect of acute exercise on insulin signaling and protein kinase B (Akt) pathways. Activation of proximal proteins involved in insulin signaling (insulin receptor, insulin receptor substrate-1 (IRS-1), phosphoinoside-3 kinase (PI3K)) are unchanged in response to acute exercise/contraction, while activation of Akt and of its substrates, TBC1 domain family 1 (TBC1D1), and TBC domain family 4 (TBC1D4) increases in response to such exercise/contraction. A wide array of Akt substrates is also regulated by exercise. Additionally, AMP-activated protein kinase (AMPK) seems to be a main mediator of the benefits of exercise on skeletal muscle. Questions persist on how mTORC1 and AMPK, two opposing regulators, are both upregulated after an acute bout of exercise

Linkage between Neighborhood Social Cohesion and BMI of South Asians in the Masala Study

Introduction. South Asians in the United States have a high prevalence of obesity and an elevated risk for cardiometabolic diseases. Yet, little is known about how aspects of neighborhood environment influence cardiometabolic risk factors such as body mass index (BMI) in this rapidly growing population. We aimed to investigate the association between perceived neighborhood social cohesion and BMI among South Asians. Methods. We utilized cross-sectional data from the MASALA study, a prospective community-based cohort of 906 South Asian men and women from the San Francisco Bay area and the greater Chicago area. Multivariable linear regression models, stratified by sex, were used to examine the association between perceived level of neighborhood social cohesion and individual BMI after adjusting for sociodemographics. Results. Participants were 54% male, with an average age of 55 years, 88% had at least a bachelor’s degree, and the average BMI was 26.0 kg/m2. South Asian women living in neighborhoods with the lowest social cohesion had a significantly higher BMI than women living in neighborhoods with the highest cohesion (β coefficient = 1.48, 95% CI 0.46–2.51, p=0.02); however, the association was not statistically significant after adjusting for sociodemographic factors (β coefficient = 1.06, 95% CI −0.01–2.13, p=0.05). There was no association between level of neighborhood social cohesion and BMI in South Asian men. Conclusion. Perceived neighborhood social cohesion was not significantly associated with BMI among South Asians in our study sample. Further research is recommended to explore whether other neighborhood characteristics may be associated with BMI and other health outcomes in South Asians and the mechanisms through which neighborhood may influence health

Aromatic Plants: use and nutraceutical properties

In the last years it has progressively been observed a substantial increase in the use of aromatic herbs and essential oils. Mediterranean area represents a particular environment in which many constraint factors (high light, temperature, drought, salinity, air pollution, etc.) induce a wide range of secondary metabolites in plants. These compounds can be useful utilized by humans for different applications: antibiotics, antimycotic, animal nutrition, cosmetics, food additives, biorepellents, etc. This paper reviews the literature on recent agro-industrial applications of Mediterranean plant species and medicinal plants used for the treatment of infectious diseases. The review includes accounts of extracts, essential oils and other active principles isolated from plants that have been used by folk medicine as antimicrobial agents. The name and part of the studied plants, spectrum of activity, type of active compounds and methods used are discussed and their mechanisms of action as well