Prenatal dexamethasone and postnatal high-fat diet have a synergistic effect of elevating blood pressure through a distinct programming mechanism of systemic and adipose renin–angiotensin systems

Abstract

BackgroundHypertension may result from high-fat (HF) diet induced-obesity and overexposure to glucocorticoids in utero. Recent studies demonstrated the potent contribution of adipose tissue’s renin-angiotensin system (RAS) to systemic RAS, which plays a key role in regulating blood pressure (BP). In this study, we investigated the effects of prenatal dexamethasone (DEX) exposure and postnatal HF diet on RAS of adipose tissue.MethodsRAS and BP of 6-month old rats exposed to prenatal DEX and/or postnatal HF diet were examined.ResultsPrenatal DEX plus postnatal HF exerted a synergistic effect on systolic BP. Prenatal DEX exposure suppressed plasma angiotensin (ANG) I and ANG II, whereas postnatal HF suppressed plasma ANG-(1–7) level. Prenatal DEX increased prorenin receptor and renin levels, but suppressed angiotensinogen (AGT) and angiotensin-converting-enzyme 1 (ACE1) mRNA expressions in adipose tissue. Postnatal HF increased AGT mRNA expression, but suppressed prorenin receptor, renin, ACE2, ANG II type 2 receptor (AT2R), and Mas receptor (MasR) mRNA expression levels.ConclusionsPrenatal GC exposure altered the ACE1/ANG II/ANG II type 1 receptor (AT1R) axis, whereas postnatal HF negatively impacted the ACE2/ANG-(1–7)/MasR axis. Prenatal DEX exposure and postnatal HF synergistically elevated BP through a distinct programming mechanism of systemic and adipose RAS. Adipose RAS might be a target for precise hypertension treatment.Electronic supplementary materialThe online version of this article (10.1186/s12944-018-0701-0) contains supplementary material, which is available to authorized users.

Biological plausibility for interactions between dietary fat, resveratrol, ACE2, and SARS-CoV illness severity

“…The mRNA levels in mice livers were assessed, and it was observed that ACE2 gene expression was reduced in the HFD group compared with the control group (11). Similarly, another study in the retroperitoneal adipose tissue of postnatal rats found that consumption of an HFD downregulated ACE2 gene expression (41). Research has also demonstrated that an HFD can lead to reduced kidney ACE2 activity only in male mice and further demonstrated that the ovariectomy of female mice fed an HFD led to reduced adipose ACE2 activity (13).…”

“…With ACE2 as the cellular receptor for SARS-CoV, the interaction between the virus and ACE2 impacts its entrance and clearance (29,45). ACE is responsible for the cleavage of AngI into AngII (34,37), and following this process, ACE2 generates Ang (16,23,29,30,39,41,43) from a single residue cleavage of AngII and then acts as a negative regulator (8). This phenomenon has been demonstrated in mouse models, whereby disrupting the murine ACE2 gene leads to increased levels of AngII (6).…”

“…As such, the ACE2 cellular receptor has been proposed as a key target for the therapeutic treatment of SARS-CoV (41,43). The virus has a strong binding affinity to human ACE2 (22), and ACE2 is required for host cell entry and viral replication (43).…”

“…The vast majority of the research on the impact of dietary intake on ACE2 activity has focused on dietary fat intake. Within these studies, the amount of dietary fat in the high-fat diet (HFD) groups varies from~50 to 60% of total energy intake (11)(12)(13)41). In a 10-wk dietary intervention study in mice, ACE2 gene expression was examined in a control group (76% carbohydrate, 14% protein, 10% lipids) and an HFD group, in which the HFD was rich in saturated fat (36% carbohydrate, 14% protein, 50% lipids).…”

“…Emerging research has demonstrated that dietary intake can impact the expression and function of the ACE2 gene (30,41). Given our knowledge of the importance of ACE2 for SARS-CoV pathogenesis, coupled with preliminary knowledge about the impact of nutrition on ACE2 gene expression and function, the purpose of this paper is to present the evidence for the biological plausibility of gene-diet interactions with ACE2 modulating SARS-CoV illness severity.…”