Background

Adipocytes are a storage site for retinol and function as antigen presenting cells (APCs) to stimulate AT-Tregs, which are key determinants of insulin sensitivity. While AT-Tregs are reduced in obesity, we unexpectedly found AT-Tregs decreased after bariatric surgery (BS). Given retinol’s role in Treg differentiation, we hypothesize that post-operative vitamin A deficiency contributes to this reduction. We determined changes in Ad retinol-associated (RA) gene expression after BS and their association with plasma retinol and APC genes.

Methods

Subcutaneous Ad were isolated at the time of BS and 12 months post-operatively (n=24) and evaluated for genes related to retinol (LRAT, RDH, BCMO1, ALDH1A, RBP1-6) and APC (CIITA, CD80, CD74, CD86, HLA-DPA1). AT-Treg abundance (CD4+/CD25+/FOXP3+) was characterized using flow cytometry.

Results

Retinol binding proteins (CRBP1,5) and storage enzymes (LRAT) were significantly reduced in Ad after BS, suggesting reduced Ad retinol. Ad-RBP4, which binds plasma retinol, was increased post-operatively (2.8 vs 1.1, p=0.0007) but inversely correlated to plasma retinol (R= -0.67, p=0.02). Ad-LRAT positively correlated to Ad-CD80 (R=+0.69, p=0.01) and Ad-CD86 (R=+0.65, p=0.03), both important for Treg differentiation, while Ad-RBP4 inversely correlated to Ad-CD80 (p=0.0003) and Ad-CD86 (p=0.0004). Finally, the reduction in AT-Tregs was higher for patients with decreased post-operative plasma retinol compared to those with stable or increased levels (-60.9% vs -26.9%, p=0.08).

Conclusions

Post-operative alterations in Ad gene expression suggest depleted retinol stores, which may decrease essential Treg co-activators. Along with the association between plasma retinol and AT-Treg abundance, this suggests a novel role for post-operative vitamin A supplementation.