New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

TNF-α induces vascular insulin resistance via positive modulation of PTEN and decreased Akt/eNOS/NO signaling in high fat diet-fed mice

Abstract\ud \ud Background\ud High fat diet (HFD) induces insulin resistance in various tissues, including the vasculature. HFD also increases plasma levels of TNF-α, a cytokine that contributes to insulin resistance and vascular dysfunction. Considering that the enzyme phosphatase and tension homologue (PTEN), whose expression is increased by TNF-α, reduces Akt signaling and, consequently, nitric oxide (NO) production, we hypothesized that PTEN contributes to TNF-α-mediated vascular resistance to insulin induced by HFD. Mechanisms underlying PTEN effects were determined.\ud \ud \ud Methods\ud Mesenteric vascular beds were isolated from C57Bl/6J and TNF-α KO mice submitted to control or HFD diet for 18 weeks to assess molecular mechanisms by which TNF-α and PTEN contribute to vascular dysfunction.\ud \ud \ud Results\ud Vasodilation in response to insulin was decreased in HFD-fed mice and in ex vivo control arteries incubated with TNF-α. TNF-α receptors deficiency and TNF-α blockade with infliximab abolished the effects of HFD and TNF-α on insulin-induced vasodilation. PTEN vascular expression (total and phosphorylated isoforms) was increased in HFD-fed mice. Treatment with a PTEN inhibitor improved insulin-induced vasodilation in HFD-fed mice. TNF-α receptor deletion restored PTEN expression/activity and Akt/eNOS/NO signaling in HFD-fed mice.\ud \ud \ud Conclusion\ud TNF-α induces vascular insulin resistance by mechanisms that involve positive modulation of PTEN and inhibition of Akt/eNOS/NO signaling. Our findings highlight TNF-α and PTEN as potential targets to limit insulin resistance and vascular complications associated with obesity-related conditions.This work was supported by grants from Fundação de Amparo à Pesquisa\ud do Estado de São Paulo (FAPESP 2013/08216-2-CRID), Coordenação de Aper‑\ud feiçoamento de Pessoal de Nível Superior (CAPES) and Conselho Nacional de\ud Desenvolvimento Científico e Tecnológico (CNPq), Brazil

A Judgment Analysis of Psychological Contracts: Priorities of Part-Time and Full-time Employees in Relation to Fulfillment and Obligation to Stay

Background and Objectives: The recent recession impacted the U.S. workforce in many ways. One of the significant changes that occurred was an increase in part-time employment. Research has shown that part-time employees who are satisfied with their organizations display similar positive organizational behaviors as their full-time peers, such as increased productivity, organizational citizenship behaviors, and intent to stay with the organization. Because of this, understanding how to fulfill the needs of part-time employees can impact organizational success. In this study, a psychological contract framework was used to examine the reciprocal relationship between part-time employees and their organizations. This study explored (1) what components are prioritized when forming a psychological contract, and (2) whether part-time employees prioritize different components than full-time employees. Methodological Approach: A multi-level methodology was used. First, a policy-capturing approach was applied to examine the relative importance of psychological contract components in relation to perceptions of fulfillment and commitment. Second, a between-subjects analysis examined pattern differences based on employment status. An additional between-persons analysis explored the interactive relationship between employment status and job involvement. Findings: The proposed psychological contract components all receive a significant weight by respondents when rating fulfillment and commitment. Additionally, differences were evident by employment status. Of note, part-time respondents gave much greater weight to the ability to control their own schedule and work-life balance. Results for the interaction between employment status and job involvement were less conclusive. Conclusions: This study suggests that part-time employees do have distinct psychological contracts from full-time employees. Researchers and practitioners can use this information to create more fulfilling work experiences for this growing segment of the workforce