Hindsight: Adipose Tissue Renin-Angiontensin SystemSaturday, January 14, 2012
Continuing in my series of Saturday posts on some of my previous work on obesity, here is a paper that I am particularly fond of, as it started me off on a whole new line of research, namely studying the potential link between obesity and the key system involved in sodium homeostasis.
Prior to this paper, published in the Journal of Hypertension in 1999, I had already done extensive work on the relationship between salt intake and blood pressure and was quite interested in answering the question why obesity promotes sodium retention, volume expansion, and an increase in blood pressure.
Leptin had been discovered a few years ago and we were beginning to consider fat cells as endocrine cells – although many of the ‘adipokines’ now known to be produced by fat cells had yet to be discovered.
Interestingly, I happened to come across a paper suggesting that, in rats, adipose tissue may make angiotensinogen, the substrate for renin, which generates angiotensin 1, which in turn, is converted by angiotensin converting enzyme (ACE) to angiotensin 2. This is one of the most powerful pressor hormones and has a wide range of effects mediated through angiotensin type 1 and type 2 receptors. Medications like ACE and angiotensin receptor blockers (ARBs) are now amongst the most widely used blood pressure lowering medications.
Thus, I wondered whether human adipose tissue likewise produces angiotensinogen and perhaps other components of this system. So I approached a surgical colleague (Norbert Runkel) and requested his help in obtaining some human fat tissue, which my student Stefan Engeli then used to demonstrate, that human adipocytes do in fact express all components of the renin angiotensin system.
We not only demonstrated the ample expression of angiotensinogen, renin, renin-binding protein, angiotensin converting enzyme, chymase and type 1 and type 2 angiotensin receptors in RNA extracted from whole adipose tissue (subcutaneous and omental) but also in isolated cultured human adipocytes (mammary).
Not only did these findings clearly demonstrate (for the first time) the presence of a local renin-angiotensin system in human adipose tissue, but also prompted us to speculate that this local renin-angiotensin system may well be involved in obesity-related disorders, including hypertension and the metabolic syndrome.
Since then, we and others have done more work on this system – more on that in future posts.
According to Google Scholar, this paper has been cited 145 times.
Engeli S, Gorzelniak K, Kreutz R, Runkel N, Distler A, & Sharma AM (1999). Co-expression of renin-angiotensin system genes in human adipose tissue. Journal of hypertension, 17 (4), 555-60 PMID: 10404958