Abstract 3205: Pro-Inflammatory Phenotype Of Perivascular Adipocytes: Influence Of High Fat Feeding
Recent studies indicate that adipose tissue depots are functionally diverse and originate from distinct precursor cells. The functions of these depots, and their capacity to modulate local disease processes, remain to be determined. Perivascular adipocytes reside at the adventitial border of blood vessels and can regulate vascular contractility; however, the molecular and biochemical properties of perivascular adipocytes are unknown. Human perivascular adipose tissues and differentiated perivascular adipocytes isolated from non-diseased blood vessels were compared with subcutaneous and visceral (perirenal) adipose tissues and differentiated adipocytes, respectively. Perivascular adipocytes were smaller than subcutaneous and perirenal adipocytes in situ and accumulated less lipid droplets when differentiated in vitro. This was accompanied by reduced expression of adipocyte-associated genes PPARγ, C/EBPα, FABP4, and adiponectin (an anti-inflammatory adipokine), suggesting a reduced state of adipocytic differentiation. In contrast, perivascular adipocytes expressed and released more pro-inflammatory IL-8 and IL-6, and secreted up to 40-fold higher levels of MCP-1, as compared with subcutaneous and perirenal adipocytes. Murine perivascular adipose tissues likewise expressed lower levels of adipocyte-associated genes as compared with subcutaneous and visceral adipose tissues. Following two weeks of high fat feeding, expression of anti-inflammatory adiponectin, PPARγ, and FABP4 genes declined further in perivascular adipose tissues. We conclude that perivascular adipocytes exhibit impaired differentiation and a heightened pro-inflammatory state, properties that are intrinsic to the adipocytes residing in this depot. Dysfunction of perivascular adipose tissue induced by high fat diet suggests that this unique adipose depot is capable of linking metabolic signals to inflammation in the blood vessel wall.