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

Abstract

Aims/hypothesis 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 B 6 (pyridoxal 5-phosphate [PLP]), known to be generated through pyridoxal kinase (PDXK), and adipogenesis. Methods 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.Results 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 increased SAT PDXK mRNA levels in parallel with adipogenic genes. In human pre-adipocytes, PDXK mRNA levels increased during adipocyte differentiation and after administration of peroxisome proliferator-activated receptor-γ agonists, and decreased under inflammatory stimuli. Mechanistic studies in 3T3-L1 cells showed that PLP administration resulted in increased adipogenic mRNA markers during early adipogenesis, whereas the PLP antagonist 4-deoxypyridoxine exerted opposite effects. Conclusions/interpretation Overall, these results support the notion that in situ production of PLP is required for physiological adipogenesis.

Microbiota and metabolome responses in the cecum and serum of broiler chickens fed with plant essential oils or virginiamycin

“…In addition, PEO treatment increases the biosystem of Pyridoxal (VB6) and Pantothenate in the cecal contents. Pyridoxal participates protein and sugar metabolism 57 , and the active form of VB6 is linked with adipogenesis 58 . These results indicate that PEO might alter different lipid metabolites and vitamins from AGP.…”

Differential fecal microbiota are retained in broiler chicken lines divergently selected for fatness traits

“…The higher activity of methanogenesis is in line with the higher relative abundances of methanogenic archaea in the FL samples. A recent study found that the active form of vitamin B6 (pyridoxal 5-phosphate) is linked with adipogenesis using a comparative metabolomic approach76.…”

Lentivirus-mediated microRNA-124 gene-modified bone marrow mesenchymal stem cell transplantation promotes the repair of spinal cord injury in rats

“…Metabolic disorder of PDXK activity can result in metabolic disorder of amino acids, which may be the pathogenesis of the secondary injury of nervous system and other neurological damage. 20, 21 PDXK is distributed in the cytoplasm of spinal cord neurons and glial cells, which maintain the dynamic equilibrium of the pyridoxal phosphate concentration to restore stability of the SCI microenvironment, and PDXK is also the target protein for miR-124 to inhibit. 22 Therefore, it was found that miR-124 was a negative regulator of PDXK, and it conferred an inhibitory effect on PDXK expression.…”