Cardiovascular and reproductive effect of high fat diet in female mice

Obesity is a global epidemic strongly associated with cardiovascular diseases, including hypertension. Our previous research demonstrated that male mice exposed to a high-fat diet (HFD) exhibit increased heart rate (HR) and impaired parasympathetic function. The objective of the current study was to investigate how HFD affects cardiovascular health in female mice, before and during pregnancy, and its impact on the offspring. We hypothesize that HFD consumption will lead to significant cardiovascular dysfunction in female mice, which could be exacerbated during pregnancy and postpartum, adversely impacting the health of the offspring. Female C57BL/6J mice at 8 weeks of age were assigned to either a HFD (60 kcal% fat) or a regular diet (RD, 22 kcal% fat). Echocardiography was conducted to evaluate changes in cardiac structure and function, and radiotelemetry was employed to monitor changes in blood pressure (BP), HR, baroreflex sensitivity, and autonomic function. Glucose Tolerance Tests (GTT) were conducted to assess metabolic function in response to HFD. Following 12 weeks of dietary exposure, the females were paired with males (previously fed RD), and telemetry monitoring was conducted weekly throughout pregnancy. Our results show that HFD-exposed females exhibited impaired cardiac function both before and after pregnancy with reduced ejection fraction (before mating: 73.02% in RD vs. 64.5% in HFD, p<0.001; at postpartum: 72.96% in RD vs 66.86% in HFD, p<0.01) and fractional shortening (before mating: 41.28% in RD vs. 34.45% in HFD, p<0.001; at postpartum: 41.32% in RD vs. 36.49% in HFD, p<0.01). The 24-h telemetry recordings revealed that HFD exposure led to significantly elevated BP (Systolic BP: 103.8 mmHg in RD vs. 116.9 mmHg in HFD, p<0.01) and HR (470 bpm in RD vs. 551.9 in HFD, p<0.001) before pregnancy. In addition, HFD-exposed females exhibited reduced spontaneous baroreflex sensitivity (SBRS) (3.169 ms/mmHg in RD vs 2.236 ms/mmHg in HFD, p<0.01) and dampened parasympathetic tone (HR increase following atropine i.p. injection: 274.1 bpm in RD vs 143.4 bpm in HFD, P< 0.01). Pregnancy resulted in reduced baroreflex sensitivity and increased BP (weeks 2 and 3) in RD controls (Week 2: SBRS= 2.302 ms/mmHg, SBP= 112.9 mmHg; Week 3: SBRS=2.388 ms/mmHg, SBP= 115.8 mmHg), and both parameters were further exacerbated by HFD (Week 2: SBRS= 1.716 ms/mmHg, SBP= 120.3 mmHg; Week 3 SBRS= 2.023 ms/mmHg, SBP= 121.4 mmHg). HFD exposure also resulted in metabolic dysfunction with significantly increased blood glucose levels both before and during pregnancy and reduced glucose tolerance compared to RD-fed controls (blood glucose AUC; before mating: 32,013 in RD vs. 48,828 in HFD, P< 0.001; at postpartum: 27,681 in RD vs. 53,771 in HFD, P < 0.01). Finally, although HFD exposure did not affect the success rate of pregnancy and delivery, most of the pups (78.2%) died during the first three days following birth compared to the RD group (18.5%), and the cause of these early deaths remains unknown. In summary, our study highlights that chronic exposure to HFD leads to impaired cardiovascular and autonomic function in female mice, which is further exacerbated during pregnancy, and the above effects are associated with reduced survival of the offspring. This work is supported by R01HL150592 This abstract was presented at the American Physiology Summit 2025 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.