In vitro studies of the renin-angiotensin system in human adipose tissue/adipocytes and possible relationship to SARS-CoV-2: a scoping review

Abstract

The renin-angiotensin system (RAS) operates within adipose tissue. Obesity-related changes can affect adipose RAS, predisposing to hypertension, type 2 diabetes, and possibly severe COVID-19. We evaluated the in vitro research on human adipose RAS and identified gaps in the literature. Medline (Ovid), Embase (Ovid), Web of Science, Scopus, and 1findr were searched to identify relevant studies. Fifty primary studies met our inclusion criteria for analysis. Expression of RAS components ( n = 14), role in differentiation ( n = 14), association with inflammation ( n = 15) or blood pressure ( n = 7) were investigated. We found (1) obesity-related changes in RAS were frequently studied (30%); (2) an upswing of articles investigating adipose ACE-2 expression since the COVID-19 pandemic; (3) a paucity of papers on AT2R and Ang (1–7)/MasR which counterbalance Ang II/ART1; (4) weight loss lowered adipose ACE-2 mRNA expression; and (5) angiotensin receptor blockers (ARBs) reduced deleterious effects of angiotensin II. Overall, these studies link Ang II/ATR1 signalling to impaired adipogenesis and a pro-inflammatory dysfunctional adipose tissue, with ATR1 blockade limiting these responses. ACE-2 may mitigate Ang II effects by converting it to Ang(1–7) which binds MasR. More work is needed to understand adipose RAS in various pathologic states such as obesity and COVID-19 infection.T.

ACE2 and TMPRSS2 expression in patients before, during, and after SARS-CoV-2 infection

“…A notable limitation is that the samples used in this study represented nasopharyngeal cells; however, ACE2 is highly expressed in the human body ( Hamming et al., 2007 ; Hikmet et al., 2020 ), with abundant expression in the heart and small intestine tissues ( Hikmet et al., 2020 ; Li et al., 2020 ), as well as the adipose tissue, where the harmful effects of ang II are present in the form of inflammation and adipogenesis ( Ting et al., 2023 ). Because ACE2 is widely expressed in human tissues ( Hamming et al., 2004 ; Ni et al., 2020 ; Beyerstedt et al., 2021 ), the potential effects of lower or higher ACE2 expression may occur within other tissues, possibly influencing COVID-19 symptoms, considering that it infects such important tissues to maintain homeostasis ( Wu et al., 2020 ; Gasmi et al., 2021 ).…”

The Relationship between Renin–Angiotensin–Aldosterone System (RAAS) Activity, Osteoporosis and Estrogen Deficiency in Type 2 Diabetes

“…Furthermore, the upregulation of RAAS induces insulin resistance in adipose tissue [30]. In T2D, the renin-encoding gene is expressed and upregulated in adipose tissue, which also contains Cathepsin D and G enzymes that can create Ang I and Ang II via RAAS alternate pathways [32]. Nutrition was proposed as the link between RAAS upregulation and hyperglycemia.…”