ABSTRACT
BACKGROUND: Interventions for T2DM have in part aimed to mimic exercise. Here, we have compared the independent and combined effects of a PPARdelta agonist and endurance training mimetic (GW501516) and a myostatin antibody and resistance training mimetic (PF-879) on metabolic and performance outcomes in obese insulin resistant mice. METHODOLOGY/PRINCIPAL FINDINGS: Male ob/ob mice were treated for 6 weeks with vehicle, GW501516, PF-879, or GW501516 in combination with PF-879. The effects of the interventions on body composition, glucose homeostasis, glucose tolerance, energy expenditure, exercise capacity and metabolic gene expression were compared at the end of study. GW501516 attenuated body weight and fat mass accumulation and increased the expression of genes of oxidative metabolism. In contrast, PF-879 increased body weight by driving muscle growth and altered the expression of genes involved in insulin signaling and glucose metabolism. Despite their differences, both interventions alone improved glucose homeostasis. Moreover, GW501516 more effectively improved serum lipids, and PF-879 uniquely increased energy expenditure, exercise capacity and adiponectin levels. When combined the robust effects of GW501516 and/or PF-879 on body weight, adiposity, muscle mass, glycemia, serum lipids, energy expenditure and exercise capacity were highly conserved. CONCLUSIONS/SIGNIFICANCE: The data, for the first time, demonstrate postnatal inhibition of myostatin not only promotes gains in muscle mass similar to resistance training,but improves metabolic homeostasis. In several instances, these effects were either distinct from or complimentary to those of GW501516. The data further suggest that strategies to increase muscle mass, and not necessarily oxidative capacity, may effectively counter insulin resistance and T2DM.
Subject(s)
Energy Metabolism , Insulin Resistance , Myostatin/antagonists & inhibitors , Obesity/metabolism , PPAR delta/agonists , Adiponectin/metabolism , Animals , Antibodies, Monoclonal/immunology , Body Composition , Citrate (si)-Synthase/metabolism , Gene Expression Regulation , Glucose/metabolism , Homeostasis , Insulin/metabolism , Lipid Metabolism , Male , Mice , Mice, Inbred C57BL , Myostatin/immunology , Physical Conditioning, Animal , Polymerase Chain Reaction , Triglycerides/metabolismABSTRACT
Existing methods to quantify angiogenesis range from image analysis of photographs to fluorescent microscopy. These methods are often time consuming and costly; they also may not detect capillaries if they are indistinct from the background of the image. We have developed a simple method based on the motion of blood to create an image that reveals the entire angiogenic vasculature. Two image analysis software programs were used separately to demonstrate the method. Using either ImageJ or Environment for Visualizing Images, we analyzed a video clip of regenerated tissue from the partially amputated caudal fin of a zebrafish (Danio rerio). The deviations among the frames in the video stack were calculated to reveal pixels where motion has occurred. The resulting image highlighted all vessels through which blood flowed and allowed for automatic quantification of the newly developed vasculature. Using this method, we quantified the angiogenic action of basic fibroblast growth factor and vascular endothelial growth factor, as well as suppression of angiogenesis by an inhibitor. In a preliminary study, we also found that it could be used to trace the developing vasculature in zebrafish embryos. Thus, motion-based angiogenesis analysis may provide an easy and accurate quantification of angiogenesis.