Coxsackie and adenovirus receptor is increased in adipose tissue of obese subjects: a role for adenovirus infection?

Abstract

The coxsackie and adenovirus receptor (CAR) was originally identified as a common receptor for coxsackie B viruses and type C adenoviruses. The objective was to investigate CAR gene expression in human adipose tissue to explore its associations with adipocyte physiology. This was an ex vivo study in 91 visceral adipose tissue (VAT) and 109 sc adipose tissue (SAT) human samples (61 paired) obtained during elective surgical procedures. Patients were recruited at the Endocrinology Service of the Hospital Universitari Dr Josep Trueta. CAR mRNA was measured in human adipose tissue samples and confirmed at the protein level and in adipose tissue fractions. The effects of inflammatory stimuli on CAR gene expression were also evaluated. In paired samples, CAR was 46-fold higher in VAT vs SAT (P < .0001), being higher also at the protein level (P = .04). CAR was predominantly found in stromal vascular cell fractions (SVFs) in both fat depots. CAR mRNA (P = .006) and protein levels (P = .01) in VAT were significantly increased in obese vs nonobese subjects. In fact, CAR mRNA levels in SAT were positively associated with body mass index (r = 0.26; P = .008) and percentage fat mass (r = 0.28; P = .004). In VAT, MGLL, FSP27, AKAP, omentin, TKT, S14, and FABP contributed independently to CAR mRNA variation after adjusting for age and body mass index. Macrophage-conditioned medium led to increased CAR gene expression in mature adipocytes in vitro. The increased expression of CAR in adipose tissue from obese subjects, mainly in SVFs, suggests that CAR might play a role in adipose tissue dysfunction, given its dual associations with adipogenic and inflammatory genes.