Endocrine Abstracts

Vitamin B12 (B12) is an essential micronutrient required for optimal hematopoietic, neurologic and other several metabolic reactions. Longitudinal studies and animal models showed that low maternal vitamin B12 deficiency is associated with the maternal obesity, development of insulin resistance and metabolic syndrome phenotype suggesting the crucial role of B12 in adipose tissue function. Although the mechanisms underpinning metabolic disorders remain poorly defined, the pathophysiology of obesity-induced metabolic diseases has been strongly related to white adipose tissue dysfunction through several mechanisms such as fibrosis, apoptosis and inflammation. Therefore, the aim of this study is to investigate the role of B12 inflammation in human adipocytes. Human pre-adipocytes cell line (Chub-S7) and primary adipocytes were obtained from lean, obese and morbid obese patients, grown to confluence, differentiated for one week, maintained in nutrition media for next 7 days (day 14) and then used for further experimental analysis. In order 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. Chub-S7 and primary adipocytes cultured in low vitamin B12 conditions showed significantly increased gene expression of pro-inflammatory cytokines such as interleukin-1 (IL-1) interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-18 (IL-18), transforming growth factor beta (TGF-β), tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1/CCL2). Our data highlights that low B12 in adipocytes induces higher gene expression and secretion of pro-inflammatory cytokines, which might lead to adipocyte dysfunction. This link between vitamin B12 deficiency and metabolic inflammation opens new insights into the pathogenesis of maternal obesity and the relevance of micronutrient supplementation for pregnant mothers.