Follow-up studies show that weight gain in women proportionally increases the risk of coronary heart disease and that weight cycling is associated with adverse cardiometabolic markers. Moreover, women after menopause are prone to weight gain.

To work out a protocol responsible for weight fluctuation and to measure the cardiac functional consequences after a final weight loss, in mice having undergone or not an ovariectomy (OVX).

Five-month-old female underwent OVX or not. Starting 5 days after surgery, mice were subjected to Yoyo dieting with successive periods (I, II, III) of a biphasic alternation of a high fat diet (HFD) (4-week constant phase of HFD60%) followed by standard diet (SD) (phase of 4, 6, 10 weeks for period I, II, III, respectively). Non-OVX control (CTL) mice were maintained on SD. At the end of the last SD phase, the global metabolism was evaluated by an insulin tolerance test and echo-MRI, the blood pressure was measured by plethysmography, the exercise capacity was evaluated on treadmill, then the left ventricular (LV) function was assessed by ultrasound and invasive hemodynamics.

Body weight in Yoyo and OVX-Yoyo mice was higher to that of CTL mice at the end of period III. Moreover, the first phase of HFD resulted in a higher weight gain in OVX-yoyo mice, which kept bigger than Yoyo mice until the end of the protocol, however without difference in body composition. There was decreased insulin sensitivity in both Yoyo and Yoyo-OVX mice compared to CTL. There was no difference in blood pressure nor in LV fractional shortening between groups. Invasive hemodynamics showed no difference in LV-end diastolic pressure (LVEDP) but an increased LV end-diastolic pressure volume relation (LVEDPVR) in OVX-Yoyo mice, indicating decreased compliance. LV weight was increased in Yoyo mice only. Treadmill stress test showed decreased running duration for OVX-Yoyo mice only (Fig. 1).

In female mice subjected to the same Yoyo diet protocol, those in post-menopausal condition after OVX show an increased risk of developing heart failure with preserved ejection fraction and reduced exercise capacity.