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Peripheral arterial disease (PAD) affects 5 million people in the US and is the primary cause of limb amputations. Exercise remains the single best intervention for PAD, in part thought to be mediated by increases in capillary density. How exercise triggers angiogenesis is not known. PPARγ coactivator (PGC)-1α is a potent transcriptional coactivator that regulates oxidative metabolism in a variety of tissues. We show here that PGC-1α mediates exercise-induced angiogenesis. Voluntary exercise induced robust angiogenesis in mouse skeletal muscle. Mice lacking PGC-1α in skeletal muscle failed to increase capillary density in response to exercise. Exercise strongly induced expression of PGC-1α from an alternate promoter. The induction of PGC-1α depended on β-adrenergic signaling. β-adrenergic stimulation also induced a broad program of angiogenic factors, including vascular endothelial growth factor (VEGF). This induction required PGC-1α. The orphan nuclear receptor ERRα mediated the induction of VEGF by PGC-1α, and mice lacking ERRα also failed to increase vascular density after exercise. These data demonstrate that β-adrenergic stimulation of a PGC-1α/ERRα/VEGF axis mediates exercise-induced angiogenesis in skeletal muscle. [ABSTRACT FROM AUTHOR]

Background. Obesity is considered a growing health threat in the United States. Although physicians have an important role in counseling their patients for obesity prevention and treatment, physicians themselves are often overweight. There are few data regarding how physician body weight might affect patient receptiveness to obesity counseling.Methods. A 43-item survey instrument was developed that consisted of three scales related to physician characteristics, health locus of control, and perceptions on receiving health advice from overweight physicians. The survey was administered to 226 patients in five physician offices. Two of the physicians were classified as obese using BMI calculations, and three were nonobese. The responses from the surveys were grouped into those from obese and nonobese physicians.Results. Significant differences were found for patient receptiveness to counseling for treatment of illness (P = 0.038) and health advice (P = 0.049), with the patients of nonobese physicians indicating greater confidence scores. The difference for weight and fitness counseling did not reach significance (P = 0.075). Analysis revealed that patient BMI was not a significant covariate nor were items related to physician characteristics in general or health locus of control.Conclusions. Patients seeking care from nonobese physicians indicated greater confidence in general health counseling and treatment of illness than patients seeing obese physicians. It is not known if this can be translated into increased success in obesity prevention and treatment. [Copyright &y& Elsevier]

Summary In the United States alone, one-third of adults and nearly one-quarter of children are clinically obese. This growing epidemic is of serious concern as obesity confers a significant risk to developing numerous chronic conditions, including cancer, diabetes, and heart disease. The alarming incidence of obesity and the rising costs of treating the associated diseases has increased the urgency of acquiring a deeper understanding of all aspects of adipocyte (fat cell) biology, including how these cells form, how they are regulated, and how increased adiposity leads to disease. Since the turn of the new century we have witnessed great progress in understanding the complexities of adipocyte function and their developmental origin. As a result, our view of adipocytes has now changed dramatically. Here, I provide a brief primer on some of the hot topics that have emerged in this field of research, which now includes aspects of endocrinology, cardiology, cancer biology, and stem cell and developmental biology. I also highlight some of the unique opportunities for therapeutic targeting of adipose tissue in metabolic disease. [ABSTRACT FROM AUTHOR]

Background and Aims: Many currently available direct-acting antiviral (DAA) regimens are less effective against HCV genotype 3 than against other HCV genotypes. The all-oral, pangenotypic DAA combination of daclatasvir (NS5A inhibitor) + sofosbuvir (nucleotide NS5B inhibitor) was studied in genotype 3-infected treatment-naive and -experienced patients (ALLY-3) who achieved rates of sustained virological response at post-treatment Week 12 (SVR12) of 90 and 86% respectively. In this analysis, we assessed whether on-treatment responses to daclatasvir + sofosbuvir in genotype 3-infected patients could predict treatment outcome., Methods: In ALLY-3, treatment-naive and -experienced patients, with or without cirrhosis, were treated with daclatasvir + sofosbuvir for 12 weeks. HCV RNA kinetics and categorical virological responses on treatment were assessed. The proportions of responders and nonresponders by study week, and time to first undetectable HCV RNA, were analysed for utility in predicting treatment outcome., Results: Overall, HCV RNA levels declined rapidly during Week 1 of treatment in both treatment-naive and -experienced cohorts. Although patients with cirrhosis had a slower initial virological response as measured by the proportion of patients with HCV RNA below the lower limit of quantification at Week 1, responses converged thereafter. Positive and negative predictive values calculated for on-treatment responses were generally comparable with the overall SVR12 rate and were therefore limited indicators of outcome. SVR12 rates were not impacted by time to first undetectable HCV RNA., Conclusions: On-treatment responses are not useful predictors of ultimate virological response to the daclatasvir + sofosbuvir regimen., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)