The adipose/circulating renin-angiotensin system cross-talk enters a new dimension.

A dipose tissue has classically been assumed to function simply as a depot storing excess metabolic fuels that can be mobilized during energy deprivation. It is now well recognized , however, that adipocytes are major players in the regulation of a large number of physiological functions including blood pressure. 1 Among ways, adipocytes influence physiological processes; it is arguably their ability to produce and secrete hormones that act in a paracrine or endocrine fashion that has reinvigorated the study of this cell type. For instance, adipocyte-derived angiotensinogen (AGT), the only known precursor of angiotensin II (Ang II), is known to contribute to the circulating pool of this protein. In the current issue of Hypertension, Yiannikouris et al 7 describe a new way by which fat can affect the circulating renin-angiotensin system (RAS) and blood pressure. The realization that essentially all components of the RAS are expressed in adipose tissue led to the notion of a local adipose RAS that may influence metabolism as well as blood pressure. 2 This was further supported by studies in humans showing positive correlations among fat mass, circulating AGT, and RAS activity 3 that are reversible by weight loss. 4 The relevance of the local adipose RAS to blood pressure control was established using genetically modified animals. For example, adipose tissue-specific transgenic expression of AGT increases blood pressure in mice. 5 Moreover, adipose tissue-restricted re-expression of AGT in global AGT knockout mice corrected the low blood pressure. 3 Conversely, Yiannikouris et al 6 have previously shown that deletion of AGT from adi-pocytes resulted in lower systolic blood pressure in C57BL/6 mice maintained on a normal chow diet. Building on this, in the current study, Yiannikouris et al 7 examined the relevance of the adipose tissue RAS to the development of obesity-associated hypertension by assessing the effect of high-fat diet in mice lacking the AGT gene only in adipose tissue. The authors found that high-fat diet increased blood pressure in wild-type mice, but not in adipocyte-specific AGT knockout animals, demonstrating the importance of adipose tissue AGT expression for the development of hypertension in obesity and suggests that the source of systemic RAS activation in obesity may be derived from adipose tissue expansion. This seems specific to hypertension because ablation of adipocyte AGT did not alter the increased heart rate caused by high-fat feeding. Interestingly, ablation of AGT from adipocytes did not alter the weight gain and …