The adipose tissue renin-angiotensin system and metabolic disorders: A review of molecular mechanisms

The renin-angiotensin system (RAS) is classically known for its role in regulation of blood pressure, fluid and electrolyte balance. In this system, angiotensinogen (Agt), the obligate precursor of all bioactive angiotensin peptides, undergoes two enzymatic cleavages by renin and angiotensin converting enzyme (ACE) to produce angiotensin I (Ang I) and angiotensin II (Ang II), respectively. The contemporary view of RAS has become more complex with the discovery of additional angiotensin degradation pathways such as ACE2. All components of the RAS are expressed in and have independent regulation of adipose tissue. This local adipose RAS exerts important auto/paracrine functions in modulating lipogenesis, lipolysis, adipogenesis as well as systemic and adipose tissue inflammation. Mice with adipose-specific Agt overproduction have a 30% increase in plasma Agt levels and develop hypertension and insulin resistance, while mice with adipose-specific Agt knockout have a 25% reduction in Agt plasma levels, demonstrating endocrine actions of adipose RAS. Emerging evidence also points towards a role of RAS in regulation of energy balance. Because adipose RAS is overactivated in many obesity conditions, it is considered a potential candidate linking obesity to hypertension, insulin resistance and other metabolic derangements.