Endocrine Abstracts

Vitamin B12 (B12) is an essential micronutrient required for two key metabolic reactions. Longitudinal studies and animal models showed that B12-deficiency during pregnancy is associated with the maternal obesity, development of insulin resistance and metabolic syndrome phenotype. Although the mechanisms underpinning low B12 and metabolic disorders remain poorly defined, it’s becoming increasingly clear that lipid dysregulation is associated with obesity and co-morbidities. The aim of this study is to investigate the role of B12 in lipid metabolism in human adipocytes. Human pre-adipocytes cell line (Chub-S7) and primary-adipocytes obtained from lean, obese and morbid obese patients were grown to confluence, differentiated for one week, maintained in nutrition media for next 7 days (day 14) and used for further experimental analysis. To analyse B12-deficiency effects, customized media with different concentrations of B12 (25 pM, 100 pM, 1 nM, 500 nM) were used. Gene-expression was performed by q-RTPCR, de-novo triglycerides synthesis was quantified using radioactive tracing technique incorporating of ¹⁴C-oleate and ß-oxidation and palmitate-induced oxygen consumption rate (OCR) was determined using seahorse XF analyser. Adipocytes cultured in low vitamin B12 conditions showed significantly increased expression of genes involved in triglyceride biosynthesis (such as ELOVL Fatty-Acid-Elongase-6 (ELOVL6), Stearoyl-CoA-Desaturase (SCD), Glycerol-3-phosphate-acyltransferase (GPAT), phosphatidate-phosphatase (LPIN1), Diacylglycerol-O-Acyltransferase 2 (DGAT2)) and a decreased ß-oxidation gene-expression (such as Fatty acid translocase (FAT/CD36), Acyl-CoA-Synthetase1 (ACSL1), Malonyl-CoA-Decarboxylase (MLYCD), Carnitine-palmitoyl-transferase1ß(CPT1-ß), Carnitine-Palmitoyltransferase-2 (CPT2), Acyl-CoA-dehydrogenase family (ACADS, ACADM, ACADL), Enoyl-CoA-hydratase-short-chain 1(ECHS1), Thiolase/Enoyl-Coenzyme-A-Hydratase (HADHB) and Acetyl-CoA-acyltransferase-2 (ACAA2)). Triglyceride biosynthesis detected by radioactive tracing technique resulted in higher levels in low B12 condition. In addition, we observed that basal and palmitate induced OCR was significantly reduced in B12 deficient cells. Our data highlights that low B12 dysregulates lipid metabolism increasing triglyceride synthesis and impairing ß-oxidation, which might lead to adipocyte dysfunction suggesting a possible role of B12-deficiency in metabolic disorders.