White to brown adipocyte transition mediated by Apigenin via VEGF-PRDM16 signaling.

Abstract

The dysregulated energy metabolism in white adipose tissues results in derangement of biological signaling resulting in obesity. Lack of vascularization in these white adipose tissues is one of the major reasons for dysregulated energy metabolism. Not much work has been done in this direction to understand the role of angiogenesis in white adipose tissue metabolism. In the present study, we evaluated the effect of angiogenic modulator in the metabolism of white adipocyte (WAC). Bioactive Apigenin was selected and its angiogenic ability was studied. Apigenin was shown to be highly proangiogenic hence the effect of Apigenin on de novo and trans-differentiation of WAT was studied. Apigenin showed enhanced de novo differentiation and trans-differentiation of mouse WAC into brown-like phenotype. To understand the effect of Apigenin on adipose tissue vasculature, coculture studies were conducted. Cross talk between endothelial cell and adipocytes were observed in coculture studies. Gene expression studies of cocultured cells revealed that browning of WAC occurred by triggering the expression of Vascular endothelial growth factor A. The study provides a new insight for inducing metabolic shift in WACs by modulation of angiogenesis in WAC microenvironment by the upregulation of PRDM16 cascade to trigger browning for the treatment of obesity.