A 60% high fat diet in male mice significantly reduced cardiac ACE2 expression compared to a control diet (0.6474 vs. 1.026; p=0.002).
Does a high fat diet alter cardiac renin-angiotensin system component expression and blood pressure in male C57BL/6J mice?
High-fat diet-induced obesity in male mice downregulates cardiac ACE2 expression, which may contribute to mild increases in blood pressure via altered renin-angiotensin system balance.
Absolute Event Rate: 0.6474% vs 1.026%
p-value: p=0.002
Obesity is a global epidemic that is highly associated with cardiovascular complications, such as hypertension. Previous studies have shown that dysregulation of the circulating renin-angiotensin system (RAS) contributes to obesity-related hypertension, via increases in vasoconstrictive angiotensin (Ang) II pathways and decreases in vasodilatory Ang-(1-7) pathways. Despite this, how obesity impacts tissue-specific expression of RAS components is poorly understood. The goal of this study was to profile the expression of RAS components within the heart of high fat diet (HFD)-induced obese versus control diet mice, and determine if changes in these components associate with elevations in blood pressure. We hypothesized that obese mice will have increased cardiac expression of Ang II components and decreased expression of Ang-(1-7) components, with this shift in the RAS balance correlating with increased blood pressure. To test this, male C57BL/6J mice were placed on a 60% HFD or control diet for 12 weeks (n=10-12 per group) prior to physiological analyses to quantify blood pressure, body composition, and glycemic control. Whole heart samples were then collected to assess gene expression using real-time quantitative polymerase chain reaction for the following RAS targets: angiotensin converting enzyme (ACE), angiotensin converting enzyme 2 (ACE2), Ang-(1-7) mas receptor (MasR), Ang II type 1 receptor variants a and b (AT1Ra and AT1Rb), and Ang II type 2 receptor (AT2R). Our findings indicate that HFD males exhibit cardiometabolic abnormalities consistent with the prior literature including increases in body weight and adiposity, mild elevations in blood pressure, hyperglycemia, insulin resistance, and glucose intolerance. We found that cardiac ACE2 expression was reduced in HFD males compared to control diet males (0.6474±0.0742 vs. 1.026±0.0755; p=0.002), with no differences in ACE expression. Further, HFD males had decreased expression of AT1R (AT1Ra: 0.7734±0.0882 vs. 1.017±0.0568; p=0.028, AT1Rb: 0.3393±0.0931 vs. 1.479±0.3400; p=0.031) and increased expression of MasR (1.796±0.2583 vs. 1.072±0.1218; p=0.017). There was a negative correlation between cardiac ACE2 expression and body mass (r2=-0.394, p=0.002) and trend for a negative correlation between cardiac ACE2 and blood pressure (r2=-0.103 p=0.146). These findings suggest that HFD-induced obesity in males downregulates cardiac ACE2 expression, which would be expected to increase Ang II and decrease Ang-(1-7) levels and could partially contribute to the mild increase in blood pressure. In response to changes in peptide levels, AT1R would be expected to downregulate and MasR to upregulate due to canonical ligand-receptor feedback inhibition, consistent with our findings. Additional work is needed to investigate obesity-related changes in RAS components in additional tissues involved in cardiometabolic regulation, as well as to examine for sex differences in these pathways. This study was supported by NIH grant R01 HL156986 and American Heart Association Undergraduate Student Fellowship Award #898925. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Marmande et al. (Fri,) conducted a other in Obesity. High fat diet (HFD) vs. Control diet was evaluated on Cardiac ACE2 expression (p=0.002). A 60% high fat diet in male mice significantly reduced cardiac ACE2 expression compared to a control diet (0.6474 vs. 1.026; p=0.002).