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Introduction: Muscle precursor cells (MPC) are integral to the maintenance of skeletal muscle and have recently been implicated in playing a role in bone repair. The primary objective of this study was to understand better the role of oxidative stress during the osteogenic differentiation of MPCs.Methods: Muscle precursor cells were treated with various combinations of ascorbic acid (AA), bone morphogenetic protein (BMP)-2, and either a superoxide dismutase analog (4-hydroxy-TEMPO [TEMPOL]) or polyethyleneglycol-conjugated catalase. Muscle precursor cell proliferation and differentiation were determined, and alkaline phosphatase activity was measured as an index of osteogenic differentiation.Results: After treatment with 200 μM AA, superoxide was increased 1.5-fold, whereas AA in combination with 100 ng/ml BMP-2 did not increase alkaline phosphatase (ALP) activity. When cells were treated with TEMPOL in combination with 100 ng/ml BMP-2 and 200 μM AA, ALP activity significantly increased.Discussion: These data suggest that increasing oxidative stress with AA induces sublethal oxidative stress that prevents BMP-2-induced osteogenic differentiation of MPCs. Muscle Nerve 59:501-508, 2019. [ABSTRACT FROM AUTHOR]

R2405 --> 745.13 --> Brown adipose tissue (BAT) is responsible for non‐shivering thermogenesis and has been found to play a role in improving whole‐body metabolism. While the beiging of white adipose tissue is a growing area of interest, the possibility of the BAT depot to "whiten" and store more triglycerides also has metabolic and subsequent health implications. Currently, there are limited studies that examine the effects of chronic stress and its ability to induce a white‐like phenotype in the BAT depot. Even fewer studies have directly compared the activation and whitening of this depot. This study examined a chronic four‐week exposure to murine stress hormone corticosterone compared to the β3‐adrenergic receptor agonist mirabegron. This allows for a direct comparison between the effect of corticosterone on whitening and the mirabegron‐induced activation in BAT of C57BL/6 male mice. Corticosterone‐treated mice had significantly higher body weight (p≤0.05) and BAT mass (p≤0.05), increased lipid droplet area (p≤0.05), were insulin resistant (p≤0.05) and had significantly elevated expression of uncoupling protein 1 (UCP‐1) in BAT (p≤0.05) while the mitochondrial content marker citrate synthase remained unchanged. This whitened phenotype has not been previously associated with increased uncoupling proteins under chronic stress and may represent a compensatory response being initiated under these conditions. Mirabegron‐treated mice had body and BAT weights comparable to controls, remained insulin sensitive, and had mitochondrial content and lipid droplet area similar to controls. Mirabegron‐treated mice also had significantly elevated expressions of UCP‐1 (p≤0.05) compared to controls, however, the elevated expression was notably less than that of the corticosterone treatment group. The possible compensatory mechanism with increased UCP‐1 in a whitened phenotype appears to elicit a stronger degree of uncoupling than the activation of BAT via the β3‐adrenergic receptor itself. The implications of BAT whitening and activation are usually thought of as opposing processes; however, this study clearly illustrates that they may intersect in ways not previously discovered. These findings further illustrate the complexity of BAT and how much is still left to be examined with this tissue. [ABSTRACT FROM AUTHOR]

This study was designed to investigate the role of interleukin-6 ( IL-6) on high-fat diet ( HFD)-induced glucose intolerance, and the response to voluntary physical activity in the prevention of insulin resistance. Six-week-old wild-type ( WT) and IL-6 knockout ( KO) mice with ( RUN) or without ( SED) access to running wheels were fed a HFD (60% from kcal) for 4 weeks. A glucose tolerance test revealed that blood glucose levels were 25-30% higher in KO RUN compared to all other groups. In WT RUN, weight gain was positively correlated with total caloric intake; however, this correlation was absent in KO RUN. In soleus muscle, there was a 2-fold increase in SOCS3 expression in KO RUN compared to all other groups. In gastrocnemius and plantaris muscles, Akt phosphorylation was 31% higher in WT RUN compared to WT SED, but this effect of running was absent in KO mice. Additionally, there was a 2.4-fold increase in leptin expression in KO RUN compared to KO SED in the gastrocnemius and plantaris muscles. In the liver, there was a 2- to 3.8-fold increase in SOCS3 expression in KO SED compared to all other groups, and AMPK α phosphorylation was 27% higher in WT mice (both RUN and SED) compared to KO mice (both RUN and SED). This study provides new insights into the role of the IL-6 in metabolism and energy storage, and highlights tissue-specific changes in early signaling pathways in response to HFD for 4 weeks. The collective findings suggest that endogenous IL-6 is important for the prevention of insulin resistance leading to type 2 diabetes. [ABSTRACT FROM AUTHOR]

R409 --> Adipose tissue has been found to exist in two predominant forms, white and brown. White adipose tissue (WAT) is the body's conventional storage organ, while brown adipose tissue (BAT) is responsible for non‐shivering thermogenesis, which allows mammals to produce heat and regulate body temperature. Studies examining BAT and its role in whole‐body metabolism have found that active BAT can lead to improved metabolic outcomes. While the beiging/ browning of WAT is a growing area of interest, the possibility of the BAT depot to "whiten" and store more triglycerides and adopt a lipid storage phenotype of WAT may have important health implications. Currently, there are limited studies that examine the direct effects of chronic stress in BAT and its ability to induce a white‐like phenotype in this adipose tissue depot. This current research aimed to determine the impact of high levels of the murine stress hormone, corticosterone, on the whitening process of BAT. Six‐week‐old male C57BL/6J mice were exposed to high levels (100µg/ml) of corticosterone in their drinking water for four weeks. The effect of the corticosterone on BAT was investigated for its impact on insulin resistance, and the expression of uncoupling protein 1 (UCP1), which is integral to the non‐shivering thermogenesis pathway. Corticosterone treatment significantly (p≤0.05) increased body weight, both WAT and BAT mass, and adipocyte size in each adipose depot. Corticosterone treatment significantly (p≤0.05) increased plasma insulin concentrations. The homeostatic model of assessment for insulin resistance (HOMA‐IR) demonstrated that the corticosterone treated mice were also significantly (p≤0.05) more insulin resistant than controls. Surprisingly, the BAT of the corticosterone treated mice had significantly (p≤0.05) higher protein expression levels of UCP1 than controls. The alterations found in our in vivo model illustrated that chronic treatment with corticosterone for 4 weeks resulted in tissue remodeling, altered glucose metabolism, and adipose tissue whitening. By understanding these altered adipocyte morphologies and metabolic phenotypes in mice under chronic stress, we will be better equipped to uncover pathological effects of metabolic diseases weighing the world down today. [ABSTRACT FROM AUTHOR]