Key points are not available for this paper at this time.
Background: For several years menopause was considered a natural event faced by women entering their 40’s. Evidence has now recognized that menopause causes a series of metabolic and vascular complications that negatively affect women later in life. Approximately, 65% of American menopausal women become overweight or obese which increases their risk of developing vascular events, such as hypertension. However, the mechanisms by which menopause leads to weight gain and vascular complications remain understudied. By using a preclinical model of menopause, our preliminary data shows that menopausal mice exhibit early weight gain and development of metabolic disorders. Therefore, we hypothesize that menopause causes an early onset of obesity and metabolic disorders that may precede the development of vascular complications. Methods: To address our hypothesis, eight-week-old female C57BL/6 mice were randomized into two experimental groups: Control/Sham Group (n=9) and Ovariectomized (OVX) group (n=8). The OVX group had their ovaries surgically removed and the Sham Group underwent surgery, but the ovaries were not removed. Metabolic parameters, including glucose metabolism and metabolic cages, and body weight were analyzed along the 20 weeks of the experimental protocol. At the terminal experiments, thoracic aortas were isolated and mounted in a wire myograph for vascular reactivity studies. Phenylephrine (PE) concentration response curves were utilized to assess vascular smooth muscle functionality. Results: After one week following the surgery, the OVX group showed a significant increase in body weight (19.4 ± 0.37g vs. 18.2 ± 0.40g controls, p<0.05), however, obesity was only confirmed in week 16 with the BMI (0.26 ± 0.003 vs. 0.24 ± 0.003 controls, p<0.05) and abdominal circumference (8.4 ± 0.14cm vs. 8.05 ± 0.06cm controls, p<0.05). Intriguingly, OVX group exhibited reduced food consumption (2.26 ± 0.11g vs. 3.36 ± 0.21g controls, p<0.05) water intake (3.11 ± 0.54 mL vs. 4.48 ± 0.18mL controls, p<0.05), fecal output (1.14 ± 0.07g vs. 2.10 ± 0.21g controls, p<0.05) and water intake (3.11 ± 0.54mL vs. 4.48 ± 0.18mL controls, p<0.05). Regarding glucose metabolism, the OVX group exhibited increased fasting glucose (125.4 ± 8.03mg/dL vs. 86.7 ± 2.67mg/dL controls, p<0.05), glucose intolerance (AUC: 39086.88 ± 2201.01 vs. 22939.56 ± 3187.55 controls, p<0.05), and increased triglycerides (116.0 ± 26.11mg/dL vs. 37.3 ± 4.23mg/dL controls, p<0.05). Vascular studies revealed a significant vascular smooth muscle dysfunction in the OVX group as evidenced by reduced aortic contractility to phenylephrine (EMax: 8.15 ± 1.1mN vs.12.3 ± 1.53mN controls, p<0.05). Conclusion: Our results reveals that menopause causes an early onset of weight gain that is not related to increased consumption of food but instead to an decreased metabolism. Menopausal mice developed central obesity, high fasting glucose, and high triglycerides, which taken together characterize metabolic syndrome that was accompanied by vascular smooth muscle dysfunction. NIH. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Matatov et al. (Wed,) studied this question.