Transcriptional control of human adipose tissue blood flow.

Abstract

Adipose tissue is highly vascularized and expresses several genes involved in vasodilatory and vasoconstrictive regulation. We took a transcriptional approach to study the relationships between adipose tissue blood flow (ATBF) and genes involved in vasoactive processes. As ATBF is impaired in obesity, we tested whether body weight interfered with the transcriptional regulation of ATBF. The mRNA content (real-time PCR) of 26 genes was quantified in subcutaneous adipose tissue biopsies from 28 healthy men with a wide range of BMI. ATBF was measured by 133Xe washout. None of the transcripts was related to fasting ATBF (ATBFF). However, the expression levels of two transcripts involved in vasodilation (natriuretic peptide receptor A/guanylate cyclase A (NPRA) and endothelial nitric oxide synthase (eNOS)) were positively associated with postprandial ATBF (r = 0.53 and r = 0.55, P < 0.01, respectively). Although BMI was negatively related to the mRNA content of NPRA and eNOS (r = -0.78 and r = -0.63, P < 0.01, respectively), the strong associations found between postprandial ATBF and the two transcripts were not affected by obesity. Several genes were subject to coordinated regulation of expression. This study demonstrates for the first time that ATBF responsiveness to nutrient intake is related to the transcription of two genes expressed in adipose tissue and directly involved in vasodilatory actions (eNOS and NPRA), suggesting that part of the regulation of ATBF is at a transcriptional level. Interestingly, these associations were not secondary to changes in BMI. We also found that certain genes involved in the regulation of ATBF are subject to coordinate regulation of expression suggesting physiological autoregulation.