Child‐level double burden of malnutrition in the MENA and LAC regions: Prevalence and social determinants

Although the prevalence of obesity has rapidly increased in the low‐ and middle‐income countries of the Middle East and North Africa (MENA) and Latin America and the Caribbean (LAC) regions, child undernutrition remains a public‐health challenge. We examined region‐specific sociodemographic determinants of this double burden of malnutrition, specifically, the co‐occurrence of child stunting and overweight, using Demographic and Health Survey and Multiple Indicator Cluster Survey data (2003–2016) from 11 countries in the MENA (n = 118,585) and 13 countries in the LAC (n = 77,824) regions. We used multiple logistic regressions to model region‐specific associations of maternal education and household wealth with child nutritional outcomes (6–59 months). The prevalence of stunting, overweight, and their co‐occurrence was 24%, 10%, and 4.3% in children in the MENA region, respectively, and 19%, 5%, and 0.5% in children in the LAC region, respectively. In both regions, higher maternal education and household wealth were significantly associated with lower odds of stunting and higher odds of overweight. As compared with the poorest wealth quintiles, decreased odds of co‐occurring stunting and overweight were observed among children from the second, third, and fourth wealth quintiles in the LAC region. In the MENA region, this association was only statistically significant for the second wealth quintile. In both regions, double burden was not statistically significantly associated with maternal education. The social patterning of co‐occurring stunting and overweight in children varied across the two regions, indicating potential differences in the underlying aetiology of the double burden across regions and stages of the nutrition transition.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154671/1/mcn12923_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154671/2/mcn12923.pd

Rôle de Wnt5a dans l'homéostasie du cholestérol et deux pathologies l'athérosclérose et l'obésité

Le déséquilibre de l homéostasie cellulaire du cholestérol dans les macrophages et les CMLv ainsi qu au niveau du tissu adipeux a plusieurs conséquences néfastes dans l organisme vivant. Au niveau de la paroi vasculaire, le déséquilibre de l homéostasie cellulaire du cholestérol induit également la formation des cellules spumeuses sécrétant un grand nombre de facteurs de croissance et de cytokines qui vont amplifier la réponse inflammatoire et contribuer ainsi au développement de la plaque d athérosclérose. De plus, dans le tissu adipeux, la modulation de l homéostasie cellulaire du cholestérol favorise l installation de l obésité. La connaissance des molécules cibles et la compréhension des mécanismes impliqués dans la régulation de l homéostasie cellulaire du cholestérol est donc primordiale pour prévenir l accumulation intracellulaire du cholestérol et la formation des plaques d athérosclérose. Le rôle de la protéine Wnt5a dans la régulation de l accumulation cellulaire de cholestérol n avait, à ce jour, pas été étudié. Nos résultats in vitro ont permis de montrer, pour la première fois, qu en présence de LRP1, Wnt5a est exprimé et pourrait réduire l accumulation cellulaire de cholestérol dans les MEFs après traitement avec un cocktail adipogénique. En plus, nous avons montré in vivo qu en présence de LRP1, Wnt5a induit l expression des gènes Sox9 et Cart1 marqueurs de la chondrogenèse et participe ainsi à l activation de programme de la différenciation chondrocytaire au niveau des lésions athéroscléreuses. In vivo, nous avons montré que la surexpression de Wnt5a au dans le tissu adipeux blanc et brun chez la souris pourrait réduire l accumulation du cholestérol dans les adipocytes. Nous avons montré que Wnt5a induit une diminution de l expression des gènes codant pour les enzymes de la synthèse du cholestérol (HMGCoA synthase 2 et HMGCoA réductase) et pour le transporteur impliqué dans l efflux du cholestérol (ABCA1) chez la souris.The imbalance of the cellular homeostasis of cholesterol in macrophages and VSMCs as well as adipose tissue has several adverse consequences in the organism. At the vessel wall, the imbalance of the cellular homeostasis of cholesterol induces the formation of foam cells secrete, many growth factors and cytokines. That amplifies the inflammatory response and contributes to the development of plate atherosclerosis. In adipose tissue, modulation of cellular homeostasis of cholesterol promotes the installation of obesity. Knowledge of target molecules and understanding of the mechanisms involved in regulating cellular homeostasis of cholesterol is essential to prevent the intracellular accumulation of cholesterol and the formation of atherosclerotic plaques. The role of Wnt5a protein in the regulation of cellular cholesterol accumulation had, to date, not been studied. In vitro, our results have shown for the first time we have shown in the presence of LRP1, Wnt5a is expressed and could reduce the cellular accumulation of cholesterol in MEFs after treatment with an adipogenic cocktail. In addition, we have shown in vivo in the presence of LRP1, Wnt5a induces the expression of genes Sox9 and Cart1 markers of chondrogenesis and thus contribute to the activation of chondrocyte differentiation program in terms of atherosclerotic lesions. In vivo, we showed that overexpression of Wnt5a in the white and brown adipose tissue in mice could reduce cholesterol accumulation in adipocytes. We demonstrated that Wnt5a induces a decrease the expression of genes encoding for enzymes involved in cholesterol synthesis (HMGCoA synthase and HMGCoA reductase 2) and the transporter involved in cholesterol efflux (ABCA1) in mice.STRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF

Identification of Putative Plant-Based ALR-2 Inhibitors to Treat Diabetic Peripheral Neuropathy

Diabetic peripheral neuropathy (DPN) is a common diabetes complication (DM). Aldose reductase -2 (ALR-2) is an oxidoreductase enzyme that is most extensively studied therapeutic target for diabetes-related complications that can be inhibited by epalrestat, which has severe adverse effects; hence the discovery of potent natural inhibitors is desired. In response, a pharmacophore model based on the properties of eplarestat was generated. The specified pharmacophore model searched the NuBBEDB database of natural compounds for prospective lead candidates. To assess the drug-likeness and ADMET profile of the compounds, a series of in silico filtering procedures were applied. The compounds were then put through molecular docking and interaction analysis. In comparison to the reference drug, four compounds showed increased binding affinity and demonstrated critical residue interactions with greater stability and specificity. As a result, we have identified four potent inhibitors: ZINC000002895847, ZINC000002566593, ZINC000012447255, and ZINC000065074786, that could be used as pharmacological niches to develop novel ALR-2 inhibitors

LRP1 Controls Intracellular Cholesterol Storage and Fatty Acid Synthesis through Modulation of Wnt Signaling.

International audienceThe low-density lipoprotein receptor-related protein LRP1 is a cell surface receptor with functions in diverse physiological pathways, including lipid metabolism. Here we show that LRP1-deficient fibroblasts accumulate high levels of intracellular cholesterol and cholesteryl-ester when stimulated for adipocyte differentiation. We demonstrate that LRP1 stimulates a canonical Wnt5a signaling pathway that prevents cholesterol accumulation. Moreover, we show that LRP1 is required for lipolysis and stimulates fatty acid synthesis independently of the noradrenergic pathway, through inhibition of GSK3beta and its previously unknown target acetyl-CoA carboxylase (ACC). As a result of ACC inhibition, mature LRP1-deficient adipocytes of adult mice are hypotrophic, and lower uptake of fatty acids into adipose tissue leads to their redistribution to the liver. These results establish LRP1 as a novel integrator of adipogenic differentiation and fat storage signals

Convergent Signaling Pathways Controlled by LRP1 (Receptor-related Protein 1) Cytoplasmic and Extracellular Domains Limit Cellular Cholesterol Accumulation

The low density lipoprotein receptor-related protein 1 (LRP1) is a ubiquitously expressed cell surface receptor that protects from intracellular cholesterol accumulation. However, the underlying mechanisms are unknown. Here we show that the extracellular (alpha) chain of LRP1 mediates TGFbeta-induced enhancement of Wnt5a, which limits intracellular cholesterol accumulation by inhibiting cholesterol biosynthesis and by promoting cholesterol export. Moreover, we demonstrate that the cytoplasmic (beta) chain of LRP1 suffices to limit cholesterol accumulation in LRP1(-/-) cells. Through binding of Erk2 to the second of its carboxyl-terminal NPXY motifs, LRP1 beta-chain positively regulates the expression of ATP binding cassette transporter A1 (ABCA1) and of neutral cholesterol ester hydrolase (NCEH1). These results highlight the unexpected functions of LRP1 and the canonical Wnt5a pathway and new therapeutic potential in cholesterol-associated disorders including cardiovascular diseases