Glucose intolerance induced by early estrogen deprivation and fructose-rich diet does not impair heart function in female rodents.

It was previously shown that a fructose-rich diet (FRD) induces prediabetes, cardiac dysfunction, and hypertrophy (CH) in males. We assessed FRD and estrogen depletion on female metabolism and cardiovascular function. Females on FRD or control diet (CD) did not develop prediabetes or cardiac dysfunction, although FRD-fed mice showed CH vs. CD. One month of ovariectomy (OVX) did not induce prediabetes, but FRD impaired glucose tolerance in OVX mice without additional metabolic or cardiac changes. Calcium transient amplitude decreased in OVX-FRD vs. SHAM-FRD, with delayed decay, suggesting reduced activity of the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA2a). Sodium-hydrogen exchanger 1 (NHE1) expression also decreased in OVX-FRD. These findings indicate estrogen loss does not cause dysfunction but modifies glycemic response to FRD, while reduced NHE1 may help preserve cardiac function. Impact statement In ovariectomized (OVX) mice, estrogen deficiency leads to insulin resistance and impaired glucose tolerance only when combined with a fructose-rich diet (FRD); neither OVX nor FRD alone is sufficient to induce these alterations. However, despite hormonal changes, OVX mice fed a FRD do not develop significant cardiac dysfunction.