Metabolomics uncovers the role of adipose tissue PDXK in adipogenesis and systemic insulin sensitivity

Diabetologia
J M Moreno-NavarreteJ M Fernandez-Real

Abstract

We aimed to investigate the potential mechanisms involved in the compromised adipogenesis of visceral (VAT) vs subcutaneous adipose tissue (SAT) using comparative metabolomics. Based on the differentially identified metabolites, we focused on the relationship between the active form of vitamin B6 (pyridoxal 5-phosphate [PLP]), known to be generated through pyridoxal kinase (PDXK), and adipogenesis. Non-targeted metabolomics analyses were performed in paired VAT and SAT (n = 14, discovery cohort). PDXK gene expression was evaluated in two validation cohorts of paired SAT and VAT samples in relation to obesity status and insulin sensitivity, and mechanistically after weight loss in vivo and in 3T3-L1 cells in vitro. Comparative metabolomics showed that PLP was significantly decreased in VAT vs SAT. Concordantly, PDXK mRNA levels were significantly decreased in VAT vs SAT, specifically in adipocytes. The decrease was specially marked in obese individuals. PDXK mRNA levels showed a strong association with adipogenic, lipid-droplet-related and lipogenic genes. At a functional level, systemic insulin sensitivity positively associated with PDXK expression, and surgically-induced weight loss (improving insulin sensitivity) led to incre...Continue Reading

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Citations

Mar 4, 2020·Biomedicines·Maria Teresa ValentiLuca Dalle Carbonare
Oct 3, 2018·Frontiers in Genetics·Chiara MeriglianoFiammetta Vernì
Feb 16, 2019·Frontiers in Physiology·Ferran ComasJosé María Moreno-Navarrete
May 28, 2020·International Journal of Molecular Sciences·Elisa Mascolo, Fiammetta Vernì
Oct 7, 2021·European Journal of Nutrition·Subhrajit BharSharmila S Mande

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