Claudin-1 as a novel target gene induced in obesity and associated to inflammation, fibrosis, and cell differentiation

Abstract

Objective: T lymphocytes from visceral and subcutaneous white adipose tissues (vWAT and sWAT, respectively) can have opposing roles in the systemic metabolic changes associated with obesity. However, few studies have focused on this subject. Claudin-1 (CLDN1) is a protein involved canonically in tight junctions and tissue paracellular permeability. We evaluated T-lymphocyte gene expression in vWAT and sWAT and in the whole adipose depots in human samples.

Methods: A Clariom D-based transcriptomic analysis was performed on T lymphocytes magnetically separated from vWAT and sWAT from patients with obesity (Cohort 1; N = 11). Expression of candidate genes resulting from that analysis was determined in whole WAT from individuals with and without obesity (Cohort 2; patients with obesity: N = 13; patients without obesity: N = 14).

Results: We observed transcriptional differences between T lymphocytes from sWAT compared with vWAT. Specifically, CLDN1 expression was found to be dramatically induced in vWAT T cells relative to those isolated from sWAT in patients with obesity. CLDN1 was also induced in obesity in vWAT and its expression correlates with genes involved in inflammation, fibrosis, and adipogenesis.

Conclusion: These results suggest that CLDN1 is a novel marker induced in obesity and differentially expressed in T lymphocytes infiltrated in human vWAT as compared with sWAT. This protein may have a crucial role in the crosstalk between T lymphocytes and other adipose tissue cells and may contribute to inflammation, fibrosis, and alter homeostasis and promote metabolic disease in obesity.

Keywords: claudin; immunometabolism; lymphocytes; obesity.