Vitamin C rescues high-fat diet-induced predisposition to metabolic dysregulation in GLUT10 deficient mouse model

Abstract

BackgroundThe development of type 2 diabetes mellitus (T2DM) is highly influenced by complex interactions between genetic and environmental (dietary and lifestyle) factors. Vitamin C (ascorbic acid, AA) has been considered as a complementary nutritional treatment for T2DM. However, evidence for the significance and beneficial effects of AA in T2DM is thus far inconclusive. We hypothesize that combined genetic and dietary factors may influence AA effects on metabolism. PurposeWe aimed to explore whether AA effects on metabolism are influenced by the combination of genetic and dietary factors. MethodsWe investigated the impacts of AA on high-fat diet (HFD)-induced metabolic dysregulation in wild type (WT) and GLUT10G128E mice. We have previously showed that genetic polymorphisms in glucose transporter 10 (GLUT10) gene are associated with a T2DM intermediate phenotype in non-diabetic population, and GLUT10G128E mice (carrying human orthologous GLUT10G128E variant) are highly sensitive to HFD-induced metabolic dysregulation. ResultsHere we show that AA has greater metabolic impacts on HFD-fed GLUT10G128E mice than HFD-fed WT mice. Remarkably, AA rescues defective epididymal white adipose tissue (eWAT) development in GLUT10G128E mice at early developmental stages. Furthermore, AA attenuates the predisposition of GLUT10G128E mice to HFD-triggered eWAT inflammation, adipokine dysregulation, ectopic fatty acid accumulation, metabolic dysregulation and body weight gain, as compared with WT mice. ConclusionsTaken together, AA has greater metabolic impacts on HFD-fed GLUT10G128E mice than HFD-fed WT mice. AA plays an important role in improving WAT development and HFD-induced metabolic dysregulation in GLUT10G128E mice. Our results suggest that proper WAT development is essential for metabolic regulation later in life. Furthermore, when considering the usage of AA as a complementary nutrition for prevention and treatment of T2DM, an individual’s genetics and dietary patterns should be taken into account.