European Association for the Study of Obesity Position Statement on the Global COVID-19 Pandemic

open18openFrühbeck, Gema; Baker, Jennifer Lyn; Busetto, Luca; Dicker, Dror; Goossens, Gijs H; Halford, Jason C G; Handjieva-Darlenska, Teodora; Hassapidou, Maria; Holm, Jens-Christian; Lehtinen-Jacks, Susanna; Mullerova, Dana; O'Malley, Grace; Sagen, Jørn V; Rutter, Harry; Salas, Ximena Ramos; Woodward, Euan; Yumuk, Volkan; Farpour-Lambert, Nathalie JFrühbeck, Gema; Baker, Jennifer Lyn; Busetto, Luca; Dicker, Dror; Goossens, Gijs H; Halford, Jason C G; Handjieva-Darlenska, Teodora; Hassapidou, Maria; Holm, Jens-Christian; Lehtinen-Jacks, Susanna; Mullerova, Dana; O'Malley, Grace; Sagen, Jørn V; Rutter, Harry; Salas, Ximena Ramos; Woodward, Euan; Yumuk, Volkan; Farpour-Lambert, Nathalie

UHRF genes regulate programmed interdigital tissue regression and chondrogenesis in the embryonic limb

The primordium of the limb contains a number of progenitors far superior to those necessary to form the skeletal components of this appendage. During the course of development, precursors that do not follow the skeletogenic program are removed by cell senescence and apoptosis. The formation of the digits provides the most representative example of embryonic remodeling via cell degeneration. In the hand/foot regions of the embryonic vertebrate limb (autopod), the interdigital tissue and the zones of interphalangeal joint formation undergo massive degeneration that accounts for jointed and free digit morphology. Developmental senescence and caspase-dependent apoptosis are considered responsible for these remodeling processes. Our study uncovers a new upstream level of regulation of remodeling by the epigenetic regulators Uhrf1 and Uhrf2 genes. These genes are spatially and temporally expressed in the pre-apoptotic regions. UHRF1 and UHRF2 showed a nuclear localization associated with foci of methylated cytosine. Interestingly, nuclear labeling increased in cells progressing through the stages of degeneration prior to TUNEL positivity. Functional analysis in cultured limb skeletal progenitors via the overexpression of either UHRF1 or UHRF2 inhibited chondrogenesis and induced cell senescence and apoptosis accompanied with changes in global and regional DNA methylation. Uhrfs modulated canonical cell differentiation factors, such as Sox9 and Scleraxis, promoted apoptosis via up-regulation of Bak1, and induced cell senescence, by arresting progenitors at the S phase and upregulating the expression of p21. Expression of Uhrf genes in vivo was positively modulated by FGF signaling. In the micromass culture assay Uhrf1 was down-regulated as the progenitors lost stemness and differentiated into cartilage. Together, our findings emphasize the importance of tuning the balance between cell differentiation and cell stemness as a central step in the initiation of the so-called ?embryonic programmed cell death? and suggest that the structural organization of the chromatin, via epigenetic modifications, may be a precocious and critical factor in these regulatory events.Funding: We thank Montse Fernandez Calderon, Susana Dawalibi, and Sonia Perez Mantecon, for excellent technical assistance. This work was supported by a Grant (BFU2017-84046-P) from the Spanish Science and Innovation Ministry to J.A.M

Treatment of Diabetes with Lifestyle Changes: Diet

The present chapter critically reviews scientific evidence on the impact of the diet and its components on the metabolic control, cardiovascular risk factors, and morbidity/mortality in diabetic patients. Three main topics are included in this chapter: (1) the effects of dietary treatment on body weight control in diabetic patients; (2) the optimal dietary composition in order to achieve blood glucose control and reduce other cardiovascular risk factors associated with type 2 diabetes; (3) the effects of lifestyle modifications and dietary changes on the risk to develop type 2 diabetes. The overall body of evidence seems to confirm the efficacy of current recommendations for diabetes management. However, although dietary strategies based on structured interventions are often successful, particularly in relation to body weight control, they are not easily applicable in clinical practice and, therefore, more feasible strategies should be identified. In addition, further intervention studies focused on the effects of lifestyle on hard endpoints in diabetic subjects are needed to definitively prove the role of diet in the prevention of both cardiovascular and microvascular complications in these patients over and above their impact on weight reduction