The problem of obesity: is there a role for antagonists of the renin-angiotensin system?

摘要

Obesity is a major health problem worldwide; it is associated with more than 30 medical conditions and is a leading cause of unnecessary deaths. Adipose tissue not only acts as an energy store, but also behaves like an endocrine organ, synthesising and secreting numerous hormones and cytokines. Angiotensin Ⅱ (ANG Ⅱ) is the biologically active component of the renin-angiotensin system (RAS). The RAS is present in adipose tissue and evidence suggests that ANG Ⅱ is intimately linked to obesity. Indeed, ANG Ⅱ increases fat cell growth and differentiation, increases synthesis, uptake and storage of fatty acids and triglycerides and possibly inhibits lipolysis.Evidence obtained using genetically modified animals has shown that the amount of body fat is directly related to the amount of ANG Ⅱ, i.e., animals with low levels of ANG Ⅱ have reduced fat stores while animals with excessive ANG Ⅱ have increased fat stores. In humans, epidemiological evidence has shown that body fat is correlated with angiotensinogen, a precursor of ANG Ⅱ, or other components of the RAS. Furthermore, blocking the production and/or actions of ANG Ⅱ with drugs or natural substances decreases body fat. The decrease in body fat caused by such treatments predominantly occurs in abdominal fat depots and appears to be independent of energy intake and digestibility. Clearly, ANG Ⅱ has an important role in the accumulation of body fat and the possibility exists that treatment of obesity will be enhanced by the use of natural or synthetic substances that interfere with ANG Ⅱ.