Dietary serine supplementation exacerbates type 1 diabetes incidence and severity in non-obese diabetic (NOD) mice 3888

Abstract Description Serine is a non-essential amino acid involved in key metabolic pathways required for proliferation, antioxidant defenses and lipid synthesis. Serine metabolism is dysregulated in several pathologies such as metabolic disorders, cancer and neurodegenerative diseases. While serine supplementation mitigates type 2 diabetes (T2D) and comorbidities associated with both T1D and T2D, the impact of serine supplementation on autoimmune-driven diabetes remains unclear. Using non-obese diabetic (NOD) mice, a mouse model of autoimmune T1D, we showed that dietary serine supplementation increases T1D incidence and severity as compared to a control isonitrogenous diet. To investigate further the mechanisms at play, we analyzed immune cell proportion in the pancreas prior to disease onset. We showed increased CD8 T cell infiltration into the pancreas when mice are fed with high serine diet. Besides, serine supplementation enhances the absolute number of diabetogenic CD8 T cells specific for InsB15-23 and IGRP206-14 peptides in the spleen and the pancreas. Moreover, pancreas-infiltrated T cells produce more inflammatory cytokines such as IFN-g and TNF when mice are fed with high serine diet. Altogether, although serine supplementation mitigates T2D and associated comorbidities, our results suggest opposite effects in T1D, enhancing T cell infiltration and activation, worsening both disease incidence and severity. Topic Categories Basic Autoimmunity (BA)