Ovariectomy increases blood pressure in high-fat-fed female Schlager mice with no effect on glucose metabolism

Hypertension and diet-induced obesity are serious health concerns in post menopausal women. We aimed to investigate the impact of estrogen loss on blood pressure in postmenopausal women with high sympathetic nerve activity. We hypothesize that high-fat feeding and ovariectomy (to mimic estrogen loss) will further increase blood pressure in hypertensive Schlager mice (BPH/2J) with high sympathetic nerve activity and worsen glucose metabolism due to loss of estrogen-mediated insulin sensitivity. In our study, we used 6-month-old hypertensive BPH/2J female mice and divided them into two groups. One group was fed a low-fat diet (LF; 10 KCal% fat), and the other group was fed a high-fat diet (HF; 45 KCal% fat) for 10 weeks. Fasting blood glucose levels were measured, followed by a non-invasive tail-cuff blood pressure (BP) measurement. After control BP measurement, bilateral ovariectomy (OVX) was performed. Two weeks post-OVX surgery, in the HF-fed BPH/2J mice, the mean arterial pressure (MAP) was significantly higher in mice that underwent OVX compared to Sham controls (BPH/2J-OVX: 154 ± 34 vs. BPH/2J-Sham: 113 ± 11 mmHg; p = 0.041). In contrast, OVX had no effect on the MAP in the LF-fed BPH/2J mice. Following the BP measurement, a glucose tolerance test (GTT) was conducted to assess the impact of OVX and an HF diet on glucose metabolism. Contrary to our hypothesis, we found no change in fasting blood glucose levels or in the area under the curve with the GTT, indicating that the HF diet and OVX together had no effect on glucose handling in the hypertensive BPH/2J mice. At the end of the study protocol, adipose tissue and renal tissue were collected for staining. We found adipose tissue hypertrophy in OVX mice on HF diet compared to sham controls (BPH/2J-OVX: 3080 ± 761 vs BPH/2J-Sham: 1283 ± 181 µm 2 ; p< 0.0001). Picrosirius red staining of renal tissue confirmed an increase in per cent fibrosis in OVX mice on HF diet (BPH/2J-OVX:6.9 ± 0.7% vs BPH/2J-Sham: 3 ± 0.6%; p = 0.0003), with no change in LF-OVX mice. In summary, we found that an HF diet and OVX together increased the BP, renal fibrosis, and adipocyte size without impacting the glucose metabolism in hypertensive BPH/2J mice. In conclusion, compared to a low-fat diet, intake of a high-fat diet by post menopausal women with high sympathetic nerve activity can lead to cardiorenal complications. In the future, we will investigate the mechanism of HF-mediated cardiorenal complications using female Schlager mice. The study was supported by the Core Research Grant (CRG/2020/002228) from the Anusandhan National Research Foundation, India. GS was supported by UGC, India. 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.