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Beyond the suffering of the affected subjects, type 2 diabetes (T2D) and obesity epidemics gripping the Gulf Cooperation Council (GCC) states are expected to seriously jeopardize these nations’ economies and development due to productivity losses. Available data show that healthcare budgets in GCC nations are under tremendous pressure because of diabetes- and obesity-linked comorbidities. Furthermore, T2D, once an over-forties disease, risks becoming a whole-adult-life condition because of obesity-associated early-onset T2D and prediabetes. The incidence of T2D is set to worsen unless efficient actions are taken to fight obesity and prevent the conversion of prediabetes to T2D. There is a consensus that the concomitant increase in obesity rates drives T2D rates upward. Fighting obesity at all levels should, therefore, take center stage for the GCC nations. The battle against obesity and T2D is a long-term and complex one. Therefore, only through concerted efforts between several public and private actors, including health, economic, and urbanization agencies, food producers and retailers, schools, families, youth organizations, sports clubs, and voluntary organizations, can this battle be won. The present review tries to assess the current status of diabetes and obesity epidemics in the GCC context and take stock of some of the policies and initiatives that have been, or need to be, implemented to address their growing burden. Other information Published in: International Journal of Endocrinology License: http://creativecommons.org/licenses/by/4.0 See article on publisher's website: http://dx.doi.org/10.1155/2021/6661346

Poster by Olfa Khalifa (Hamad Bin Khalifa University), Khaoula Errafii (Mohammed VI Polytechnic University), Sama Ayoub (Weill Cornell Medicine - Qatar), Abdelilah Arredouani (Hamad Bin Khalifa University) Background: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide in part due to the obesity epidemic and insulin resistance. The mechanisms underlying the non-alcoholic steatosis are poorly understood and little information is available on the pathways responsible for the progressive hepatocellular damage that follows lipids accumulation. NAFLD research is incredibly important because its diagnosis requires the conduction of a biopsy. Accordingly, more recently biomarkers including noncoding RNAs have been investigated for their involvement in the disease. There are several types of noncoding RNAs associated with NAFLD. Long noncoding RNAs (LncRNAs), which include more than 200 nucleotides, have a role in a range of biological processes including cell proliferation, death, and differentiation. MALAT1 (metastasis associated with lung adenocarcinoma transcript 1) is a well-conserved lncRNA that has been linked to a variety of illnesses, including cancer. However, its role in hepatic steatosis and lipid accumulation is unknown. MALAT1 has recently attracted attention for its role in the evolution of diabetic complications, since it has been demonstrated that MALAT1 dysregulation contributes to the pathogenesis of diabetes and liver disease. Objective: The purpose of this study was to investigate MALAT1's effects on hepatic lipid accumulation and potential targets in presence of the GLP-1R agonist Exendin-4 (Ex-4), which has the potential to improve steatosis and even steatohepatitis. Methods: A steatosis cell model was established using HepG2 cells by treating them overnight with 400 mM oleic acid (OA). We determined the optimal concentration of OA needed to obtain saturating levels of triglycerides. Then starved the cells for 6h in DMEM containing 1% fatty-acid-free bovine serum albumin. Following the starvation, a 16h incubation in DMEM containing increasing concentrations of OA (0–500 µM) at 37 °C was performed, and steatosis was quantified by triglycerides quantification, Bodipy staining, and quantification of the expression of perilipin genes family. The transcriptomic profiling was performed using total RNA extracted from untreated, steatotic and Ex-4-treated steatotic, cells. We validated a subset of differentially expressed LncRNAs with qRT-PCR and identified the most significantly enriched cellular functions associated with the relevant LncRNAs, among them MALAT1. Finally, CD36 was silenced, and lipogenesis genes expression were quantified using q-PCR and/or western blots. Results: Treatment with 200nM Ex-4 for 3h decreased the OA-induced lipid buildup significantly (p

Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease worldwide in part due to the concomitant obesity pandemic and insulin resistance (IR). It is increasingly becoming evident that NAFLD is a disease affecting numerous extrahepatic vital organs and regulatory pathways. The molecular mechanisms underlying the nonalcoholic steatosis formation are poorly understood, and little information is available on the pathways that are responsible for the progressive hepatocellular damage that follows lipid accumulation. Recently, much research has focused on the identification of the epigenetic modifications that contribute to NAFLD pathogenesis. Noncoding RNAs (ncRNAs) are one of such epigenetic factors that could be implicated in the NAFLD development and progression. In this review, we summarize the current knowledge of the genetic and epigenetic factors potentially underlying the disease. Particular emphasis will be put on the contribution of microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) to the pathophysiology of NAFLD as well as their potential use as therapeutic targets or as markers for the prediction and the progression of the disease. Other information Published in: Disease Markers License: http://creativecommons.org/licenses/by/4.0 See article on publisher's website: http://dx.doi.org/10.1155/2020/8822859

Patients treated during leukemia face the risk of complications including pulmonary dysfunction that may result from infiltration of leukemic blast cells (LBCs) into lung parenchyma and interstitium. In LBCs, we demonstrated that transient receptor potential vanilloid type 2 channel (TRPV2), reputed for its role in inflammatory processes, exhibited oncogenic activity associated with alteration of its molecular expression profile. TRPV2 was overexpressed in LBCs compared to normal human peripheral blood mononuclear cells (PBMCs). Additionally, functional full length isoform and nonfunctional short form pore-less variant of TRPV2 protein were up-regulated and down-regulated respectively in LBCs. However, the opposite was found in PBMCs. TRPV2 silencing or pharmacological targeting by Tranilast (TL) or SKF96365 (SKF) triggered caspace-mediated apoptosis and cell cycle arrest. TL and SKF inhibited chemotactic peptide fMLP-induced response linked to TRPV2 Ca2+ activity, and down-regulated expression of surface marker CD38 involved in leukemia and lung airway inflammation. Challenging lung airway epithelial cells (AECs) with LBCs decreased (by more than 50%) transepithelial resistance (TER) denoting barrier function alteration. Importantly, TL prevented such loss in TER. Therefore, TRPV2 merits further exploration as a pharmacodynamic biomarker for leukemia patients (with pulmonary inflammation) who might be suitable for a novel [adjuvant] therapeutic strategy based on TL.Other Information Published in: Scientific Reports License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1038/s41598-018-37469-8

Failure of the heat shock response is a key event that leads to insulin resistance and type 2 diabetes. We recently showed that DNAJB3 co-chaperone is downregulated in obese and diabetic patients and that physical exercise restores its normal expression with a significant improvement of the clinical outcomes. In 3T3-L1 adipocytes, DNAJB3 has a role in improving the sensitivity to insulin and glucose uptake. In co-immunoprecipitation assays, DNAJB3 interacts with both JNK1 and IKKβ kinases. However, the functional impact of such interaction on their activities has not been investigated. Here, we assessed the effect of DNAJB3 on the respective activity of JNK1 and IKKβ in cell-based assays. Using JNK1- and IKKβ-dependent luciferase reporters, we show a marked decrease in luciferase activity by DNAJB3 in response to PMA and TNF-α that was consistent with a decrease in the translocation of p65/NF-κB to the nucleus in response to LPS. Furthermore, TNF-α-mediated IL-6 promoter activation and endogenous mRNA expression are significantly abrogated by DNAJB3 both in 3T3-L1 and C2C12 cells. The ability of DNAJB3 to mitigate ER stress and oxidative stress was also investigated and our data show a significant improvement of both forms of stress. Finally, we examined the effect of overexpressing and knocking down the expression of DNAJB3 on glucose uptake in C2C12 as well as the molecular determinants. Accordingly, we provide evidence for a role of DNAJB3 in promoting both basal and insulin-stimulated glucose uptake. Our finding reveals also a novel role of DNAJB3 in eliciting Glut4 translocation to the plasma membrane. These results suggest a physiological role of DNAJB3 in mitigating metabolic stress and improving glucose homeostasis and could therefore represent a novel therapeutic target for type 2 diabetes.Other Information Published in: Scientific Reports License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1038/s41598-019-41244-8

The prevalence of nonalcoholic fatty liver disease (NAFLD), which affects around 25% of the world’s population, has been rapidly rising along with the rate of obesity in the world. NAFLD is now the leading indicator for liver transplantation in developed countries. NAFLD is a spectrum of diseases ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), which can progress to advanced fibrosis and cirrhosis, eventually culminating in hepatocellular carcinoma. NAFLD management continues to pose challenges for patients, physicians, and healthcare systems because there is presently no approved effective pharmacotherapy. The current standard of care emphasizes intensive lifestyle interventions that include calorie restriction, increased physical activity, and weight loss. Several studies have demonstrated that weight loss of 5% or more of body weight can put NAFLD into remission. However, strict compliance and long-term effort have been an issue for many NAFLD patients precisely because of the difficulty of maintaining a sustained weight reduction. This chapter discusses the evidence supporting lifestyle intervention’s effectiveness in improving NAFLD and the barriers that hinder the implementation of lifestyle adjustments and behavior changes. Finally, a few tips to help overcome these barriers are briefly discussed.