Comparative Expression of Renin‐Angiotensin Pathway Proteins in Visceral Versus Subcutaneous Fat

Abstract

BackgroundObesity‐associated metabolic disorders have been shown to be related to body fat distribution. Specifically, increases in visceral fat are more detrimental than increases in subcutaneous fat depots. However, the underlying mechanisms through which visceral fat potentiates cardiometabolic dysregulation are not completely understood. In recent years, the presence of localized renin angiotensin system (RAS) in adipose tissue and its role in regulating blood pressure and metabolism has been recognized. Therefore, we investigated if differential expression of RAS components in visceral versus subcutaneous adipose tissue may help explain pathological effects of visceral fat.HypothesisWe hypothesized that compared to subcutaneous adipose tissue, visceral adipose tissue has increased expression of RAS proteins involved in the pro‐inflammatory and pro‐fibrotic ANGII‐AT1R pathway but attenuated expression of proteins mediating the anti‐inflammatory and anti‐fibrotic ANG1‐7‐MASR pathway.MethodsWe determined the expression of RAS proteins in paired subcutaneous and visceral (omental) adipose tissue samples from obese individuals undergoing surgery (n = 30, BMI: 46.1 ± 7.3 kg/m2, age: 46.5 ± 14.4 years) by Western blot. We examined proteins involved in 1) Ang II generation: angiotensinogen (AGT), angiotensin converting enzyme (ACE), chymase; 2) Ang1‐7 generation: ACE‐2; and 3) cellular receptors: angiotensin I receptor (AT1R), MAS receptor (MASR), and aldosterone receptor.ResultsComparison of protein expression between subcutaneous and visceral adipose tissue samples showed no changes in proteins involved in generation of angiotensin peptides, namely AGT (0.64 ± 0.57 vs. 0.33 ± 0.28, p = 0.11, n = 12), chymase (0.27 ± 0.23 vs. 0.36 ± 0.41, p = 0.77, n = 22), and ACE‐2 (0.23 ± 0.41 vs. 0.08 ± 0.09, p = 0.21, n = 15). However, ACE expression tended to be higher in subcutaneous vs. visceral fat (0.10 ± 0.06 vs. 0.06 ± 0.03, p = 0.052, n = 12). Furthermore, expression of cellular receptor AT1R was higher in subcutaneous fat (0.24 ± 0.34 vs. 0.07 ± 0.09, p = 0.03, n = 12), and MASR was lower in subcutaneous fat (0.22 ± 0.26 vs. 0.88 ± 0.99, p = 0.01, n = 20). Aldosterone receptor expression (0.21 ± 0.22 vs. 0.14 ± 0.13, p = 0.52, n = 11) was not altered in subcutaneous and visceral depots.ConclusionsProteins involved in the generation of angiotensin peptides are not differentially expressed in subcutaneous versus visceral fat depots. However, expression of cellular receptors is different such that inflammatory and fibrotic effects of RAS may be more predominant in subcutaneous fat. Therefore, RAS is likely to play a role in limiting subcutaneous fat expansion thereby leading to increased visceral fat depots. Furthermore, our findings do not support the role of visceral RAS in development and progression of cardiovascular pathology associated with increased visceral fat depots.Support or Funding InformationMAP and KRS were supported by the American Physiological Society Stride Summer Undergraduate Research Fellowship NHLBI 1 R25 HL115473‐01.