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2 In ammation as a pathogenic process in diabetes mellitus: the role of adipose tissue
and interaction with other tissues or organs
It has been proven that circulating concentrations of chronic low-grade in ammation markers in young healthy adults are not only in uenced by obesity, but also by abdominal adiposity, fasting and glucose ingestion and in some cases by sex and sexual hormones (Escobar-Morreale et al , Clin Nutr 2017)
It has also been shown that lipin-2 protein controls excessive formation of IL-1β in macrophages by di erent mechanisms, including the activation of NLRP3 in ammasome, indicating that lipin-2 is a key matter in the negative regulation of the NLRP3 in ammasome (Lordén et al , J Exp Med 2017)
It has lastly been described that the stem cells derived from mesenteric adipose tissue (ASCs) of patients with Crohn’s disease have a more proliferative, in ammatory, invasive and phagocytic phenotype than the equivalent cells of healthy donors, regardless of the clinical stage (Serena et al , Stem Cell Rep 2017)
3 Identi cation of molecular mechanisms and new therapeutic targets for the
development of personalised early interventions in diabetes mellitus
It has been proven that mitochondrial dynamics mediated by Mitofusin 1 in hypothalamic POMC neurons constitute an intrinsic mechanism for detection of nutrients and reveal an unrecognised bond between this subassembly of neurons and insulin release (Ramírez et al , Cell Metab 2017)
It has also been proven that the e ects of hepatic glycogen in the ingestion and homeostasis of glucose are mediated by the vagus nerve in mice (López-Soldado, et al , Diabetología 2017) The lack of glycogenin has also been shown to promote the accumulation of muscular glycogen, which impairs the muscular function (Testoni et al , Cell Metab 2017)
4 Identi cation of danger biomarkers for the progression of diabetes
A new metabolomic strategy for studies of stable isotope tracers based on RMN has been undertaken and validated (Vinaixa et al , Angew Chem Int Ed Engl 2017), increasing the identi cation of metabolites obtained from cell extracts
Activators of protein Mitofusin 2 have also been identi ed by means of a strategy consisting of seeking transcriptional stimulators (Miret-Casals et al , Cell Chem. Biol 2017)
60 CIBER ANNUAL REPORT 2017