How to motivate managers for CSR?: Commitment to CSR by transformational leadership in meetings

Purpose: The aim of this research is to examine how it is possible to continuously motivate managers from different departments for Corporate Social Responsibility (CSR). The goal is to investigate if and how CSR leaders can realize commitment to CSR by conducting meetings in transformational leadership style. Methodology: The study uses a combination of theoretical and empirical research. Theoretical research contracts and contrasts knowledge of the areas CSR, transformational leadership and meetings in new ways. By empirical research qualitative and quantitative data is attained by 12 interviews with CSR leaders and managers of 6 Australian organizations. Findings: Transformational leadership clearly motivates managers for CSR in meetings, because it enhances trust, understanding and commitment to CSR. All of the transformational leadership components are relevant and leaders can enhance them by specific behaviors. The motivational effects of various transformational leadership elements depend on characteristics of the audience such as position, gender, personality and experience. Practical Implications: Leaders already apply the concepts of transformational leadership, but it is recommended to increase its appliance for achieving optimal motivation. For realizing commitment leaders need to be aware of different impacts of transformational leadership elements and emphasize transformational leadership behavior in CSR meetings adjusted to the audience. Limitations: Despite the sample size corresponds to academic standards of qualitative research, there are limitations regarding the investigation of the effects of transformational leadership on different age groups, various industries, organization types or countries.Objectivo: O intuito de este trabalho de pesquisa é o de aferir a possibilidade de motivar continuadamente administradores de vários departamentos, para factores de “Corporate Social Responsibility” (CSR). O propósito é então, investigar se e como vários lideres conseguem implementar CSR através de reuniões em estilo de liderança transformacional. Metodologia: O corrente estudo usa uma combinação de investigação empírica e teórica. Em termos teóricos, é procurado comparar e contrastar conhecimento nas áreas de CSR, liderança transformacional e novas formas de reuniões. A pesquisa empírica foca-se em 12 entrevistas com lideres em CSR e administradores de 6 organizações Australianas com o fim de recolher informação quantitativa e qualitativa. Resultados: Liderança transformacional motiva claramente administradores para aplicar CRS em reuniões, pois potencia sentimentos de confiança, compreensão e compromisso. Todos os componentes presentes na liderança transformacional são relevantes. Os efeitos de tais elementos contudo dependem das características da audiência: posição, gênero, personalidade e experiencia. Implicações Praticas: Correntemente lideres já aplicam em algum grau estes conceitos. Contudo, para atingir um ponto de motivação óptima, é necessário reforçar a aplicação de tais métodos e conceitos. Para conseguir reforçar o compromisso, lideres e administradores necessitam de ter em atenção os vários elementos da liderança transformacional e ajustar os seus comportamentos á audiência presente. Limitações: Apesar do tamanho da amostra respeitar as normas acadêmicas de estudos quantitativos, esse mesmo tamanho representa uma limitação, pois não é capaz de determinar os efeitos da liderança transformacional entre faixas etárias diferentes, industrias, tipos de organizações ou Países

Effects of allicin on human Simpson-Golabi-Behmel syndrome cells in mediating browning phenotype

Introduction: Obesity is a major health problem because it is associated with increased risk of cardiovascular disease, diabetes, hypertension, and some cancers. Strategies to prevent or reduce obesity focus mainly on the possible effects of natural compounds that can induce a phenotype of browning adipocytes capable of releasing energy in the formof heat. Allicin, a bioactive component of garlic with numerous pharmacological functions, is known to stimulate energy metabolism. Methods: In the present study, the effects of allicin on human Simpson-Golabi- Behmel Syndrome (SGBS) cells were investigated by quantifying the dynamics of lipid droplets (LDs) and mitochondria, as well as transcriptomic changes after six days of differentiation. Results: Allicin significantly promoted the reduction in the surface area and size of LDs, leading to the formation of multilocular adipocytes, which was confirmed by the upregulation of genes related to lipolysis. The increase in the number and decrease in themean aspect ratio of mitochondria in allicin-treated cells indicate a shift inmitochondrial dynamics toward fission. The structural results are confirmed by transcriptomic analysis showing a significant arrangement of gene expression associated with beige adipocytes, in particular increased expression of T-box transcription factor 1 (TBX1), uncoupling protein 1 (UCP1), PPARG coactivator 1 alpha (PPARGC1A), peroxisome proliferator-activated receptor alpha (PPARA), and OXPHOS-related genes. The most promising targets are nuclear genes such as retinoid X receptor alpha (RXRA), retinoid X receptor gamma (RXRG), nuclear receptor subfamily 1 group H member 3 (NR1H3), nuclear receptor subfamily 1 group H member 4 (NR1H4), PPARA, and oestrogen receptor 1 (ESR1). Discussion: Transcriptomic data and the network pharmacology-based approach revealed that genes and potential targets of allicin are involved in ligand-activated transcription factor activity, intracellular receptor signalling, regulation of cold-induced thermogenesis, and positive regulation of lipid metabolism. The present study highlights the potential role of allicin in triggering browning in human SGBS cells by affecting the LD dynamics, mitochondrial morphology, and expression of brown marker genes. Understanding the potential targets through which allicin promotes this effect may reveal the underlying signalling pathways and support these findings

Time-Resolved Expression Profiling of the Nuclear Receptor Superfamily in Human Adipogenesis

Background: The differentiation of fibroblast-like pre-adipocytes to lipid-loaded adipocytes is regulated by a network of transcription factors, the most prominent one being the nuclear receptor peroxisome proliferator-activated receptor (PPAR) gamma. However, many of the other 47 members of the nuclear receptor superfamily have an impact on adipogenesis, which in human cells has not been investigated in detail. Methodology/Principal Findings: We analyzed by quantitative PCR all human nuclear receptors at multiple time points during differentiation of SGBS pre-adipocytes. The earliest effect was the down-regulation of the genes RARG, PPARD, REVERBA, REV-ERBB, VDR and GR followed by the up-regulation of PPARG, LXRA and AR. These observations are supported with data from 3T3-L1 mouse pre-adipocytes and primary human adipocytes. Investigation of the effects of the individual differentiation mix components in short-term treatments and of their omission from the full mix showed that the expression levels of the early-regulated nuclear receptor genes were most affected by the glucocorticoid receptor (GR) ligand cortisol and the phosophodiesterase inhibitor IBMX. Interestingly, the effects of both compounds converged to repress the genes PPARD, REV-ERBA, REV-ERBB, VDR and GR, whereas cortisol and IBMX showed antagonistic interaction for PPARG, LXRA and AR causing a time lag in their up-regulation. We hypothesize that the well-known auto-repression of GR fine-tunes the detected early responses. Consistently, chromatin immunoprecipitation experiments showed that GR association increased on the transcription start sites of the genes RARG, REV-ERBB, VDR and GR. Conclusions/Significance: Adipocyte differentiation is a process, in which many members of the nuclear receptor superfamily change their mRNA expression. The actions of cortisol and IBMX converged to repress several nuclear receptors early in differentiation, while up-regulation of other nuclear receptor genes showed a time lag due to antagonisms of the signals. Our results place GR and its ligand cortisol as central regulatory factors controlling early regulatory events in human adipogenesis that precedes the regulation of the later events by PPARG

Evaluating the process of tailoring the global HIV/AIDS practice guidelines for use in developing countries

Objective. To describe a systematic procedure for adapting, or ‘tailoring' the World Health Organisation's ‘global guidelines for the management of HIV/AIDS in adults and children' for use in two developing countries: Malawi and Barbados. Design. In order for these guidelines to achieve reproducibility, clinical flexibility, and clinical applicability, a systematic procedure is needed to tailor the guidelines to the local practice conditions of specific settings. Methods. A group of local experts in each country used a nominal group process to modify the global program on AIDS (GPA) guidelines for local use. Semantic analysis techniques, known as clinical algorithm nosology (CAN), were used to compare the two modified guidelines with the global ones to determine the extent and type of differences between sets of guidelines. Results. Standard, locally-tailored algorithm map guidelines (AMG) were developed within 4 months. CAN semantic analysis showed that guideline structure was maintained; 572/858 (66.6%) decision nodes were found to be the same in the GPA/Malawi, GPA/Barbados and Malawi/Barbados comparisons. However, different guideline versions managed patients quite differently, as evidenced by clinical algorithm patient abstraction (CAPA) scores of between 0 and 8.46 (0 = different; 8 = similar; 10 = identical). Analysis of the 197 specific differences found in these abstractions showed that 83% were in approaches to diagnosis and therapy, while the remaining 17% related to disease prevalence. Conclusions. Standard techniques involving consensus used to develop clinical guidelines can also be employed to tailor these guidelines to local settings. Semantic analysis shows that the tailoring preserves structure but may involve significant modification to the processes of clinical care that could in turn affect care outcome

THP-1 Macrophages and SGBS Adipocytes – A New Human in vitro Model System of Inflamed Adipose Tissue

Obesity is associated with an accumulation of macrophages in adipose tissue. This inflammation of adipose tissue is a key event in the pathogenesis of several obesity-related disorders, particularly insulin resistance. Here, we summarized existing model systems that mimic the situation of inflamed adipose tissue in vitro, most of them being murine. Importantly, we introduce our newly established human model system which combines the THP-1 monocytic cell line and the preadipocyte cell strain Simpson–Golabi–Behmel syndrome (SGBS). THP-1 cells, which originate from an acute monocytic leukemia, differentiate easily into macrophages in vitro. The human preadipocyte cell strain SGBS was recently introduced as a unique tool to study human fat cell functions. SGBS cells are characterized by a high capacity for adipogenic differentiation. SGBS adipocytes are capable of fat cell-specific metabolic functions such as insulin-stimulated glucose uptake, insulin-stimulated de novo lipogenesis and β-adrenergic-stimulated lipolysis and they secrete typical adipokines including leptin, adiponectin, and RBP4. Applying either macrophage-conditioned medium or a direct co-culture of macrophages and fat cells, our model system can be used to distinguish between paracrine and cell-contact dependent effects. In conclusion, we propose this model as a useful tool to study adipose inflammation in vitro. It represents an inexpensive, highly reproducible human system. The methods described here can be easily extended for usage of primary human macrophages and fat cells

Extracellular Vesicles of Hypoxic Adipocytes and Obese Subjects Reduce Insulin-stimulated Glucose Uptake

Scope We investigate the effects of extracellular vesicles (EVs) obtained from in vitro adipocyte cell models and from obese subjects on glucose transport and insulin responsiveness. Methods and results EVs are isolated from the culture supernatant of adipocytes cultured under normoxia, hypoxia (1% oxygen), or exposed to macrophage conditioned media (15% v/v). EVs are isolated from the plasma of lean individuals and subjects with obesity. Cultured adipocytes are incubated with EVs and activation of insulin signalling cascades and insulin‐stimulated glucose transport are measured. EVs released from hypoxic adipocytes impair insulin‐stimulated 2‐deoxyglucose uptake and reduce insulin mediated phosphorylation of AKT. Insulin‐mediated phosphorylation of extracellular regulated kinases (ERK1/2) is not affected. EVs from individuals with obesity decrease insulin stimulated 2‐deoxyglucose uptake in adipocytes (p = 0.0159). Conclusion EVs released by stressed adipocytes impair insulin action in neighboring adipocytes

Transcription factor Hlx controls a systematic switch from white to brown fat through Prdm16-mediated co-activation

Browning of subcutaneous white fat (iWAT) involves several reprograming events, but the underlying mechanisms are incompletely understood. Here we show that the transcription factor Hlx is selectively expressed in brown adipose tissue (BAT) and iWAT, and is translationally upregulated by beta3-adrenergic signaling-mediated suppression of the translational inhibitor 4E-BP1. Hlx interacts with and is co-activated by Prdm16 to control BAT-selective gene expression and mitochondrial biogenesis. Hlx heterozygous knockout mice have defects in brown-like adipocyte formation in iWAT, and develop glucose intolerance and high fat-induced hepatic steatosis. Conversely, transgenic expression of Hlx at a physiological level drives a full program of thermogenesis and converts iWAT to brown-like fat, which improves glucose homeostasis and prevents obesity and hepatic steatosis. The adipose remodeling phenotypes are recapitulated by fat-specific injection of Hlx knockdown and overexpression viruses, respectively. Our studies establish Hlx as a powerful regulator for systematic white adipose tissue browning and offer molecular insights into the underlying transcriptional mechanism.The transcriptional co-activator Prdm16 regulates browning of white adipose tissue (WAT). Here, the authors show that Prdm16 interacts with the transcription factor Hlx, which is stabilized in response to beta3-adrenergic signaling, to increase thermogenic gene expression and mitochondrial biogenesis in subcutaneous WAT

Lipodystrophy as a late effect after stem cell transplantation

Survivors of childhood cancer are at high risk of developing metabolic diseases in adulthood. Recently, several patients developing partial lipodystrophy following hematopoietic stem cell transplantation (HSCT) have been described. In this review, we summarize the cases described so far and discuss potential underlying mechanisms of the disease. The findings suggest that HSCT-associated lipodystrophies may be seen as a novel form of acquired lipodystrophy

MiR-107 inhibits CDK6 expression, differentiation, and lipid storage in human adipocytes

MicroRNA-107 (miR-107) plays a regulatory role in obesity and insulin resistance, but the mechanisms of its function in adipocytes have not been elucidated in detail. Here we show that overexpression of miR-107 in pre- and mature human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes attenuates differentiation and lipid accumulation. Our results suggest that miR-107 controls adipocyte differentiation via CDK6 and Notch signaling. CDK6 is a validated target of miR-107 and was downregulated upon miR-107 overexpression. Notch3, a signaling receptor involved in adipocyte differentiation, has been shown to decrease upon CDK6 depletion; Here Notch3 and its target Hes1 were downregulated by miR-107 overexpression. In mature adipocytes, miR-107 induces a triglyceride storage defect by impairing glucose uptake and triglyceride synthesis. To conclude, our data suggests that miR-107 has distinct functional roles in preadipocytes and mature adipocytes; Its elevated expression at these different stages of adipocytes may on one hand dampen adipogenesis, and on the other, promote ectopic fatty acid accumulation and reduced glucose tolerance.Peer reviewe