OBJECTIVE: To investigate whether human preadipocytes possess a complete functional renin angiotensin system. MEASUREMENTS: Gene expression of angiotensinogen, renin, renin binding protein, angiotensin converting enzyme (ACE) and angiotensin II (ang II) receptor type 1 in human preadipocytes; ACE protein and ang II production of human adipose tissue stromal cells differentiated or not in primary culture. RESULTS: All genes mentioned above were found to be expressed in human preadipocytes. ACE was translated into protein as detected by western blot. Ang II was secreted both by undifferentiated preadipocytes and immature adipocytes, and its production was signi®cantly elevated in differentiated cells. CONCLUSIONS: Preadipocytes from human adipose tissue express a functional renin angiotensin system (RAS).
During their development from progenitor cells, adipocytes not only express enzymatic activities necessary for the storage of triglycerides, but also achieve the capability to produce a number of endocrine factors such as leptin, tumor necrosis factor alpha (TNFalpha), complement factors, adiponectin/adipoQ, plasminogen activator inhibitor-1 (PAI-1), angiotensin II and others. Angiotensin II is produced from angiotensinogen by the proteolytic action of renin and angiotensin-converting enzyme; and several data point to the existence of a complete local renin-angiotensin system in adipose tissue, including angiotensin II receptors. In this study, we directly monitored the production of angiotensin II type one receptor (AT1) and angiotensin II type two receptor (AT2) proteins during the adipose conversion of murine 3T3-L1 preadipocytes by immunodetection with specific antibodies. AT1 receptors could be detected throughout the whole differentiation period. The strong AT2 signal in preadipocytes however was completely lost during the course of differentiation, which suggests that expression of AT2 receptors is inversely correlated to the adipose conversion program.
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