Effects of estrogen in preventing neuronal insulin resistance in hippocampus of obese rats are different between genders

AimThe effects of estrogen on the prevention of impaired insulin-induced long-term depression in the hippocampus and neuronal insulin signaling caused by high-fat diet (HF) were studied in male and female rats.Main methodsBoth male and female rats were fed with a normal diet (ND; 19.7% energy from fat) or a high-fat diet (HF; 59.3% energy from fat) for 12 weeks. Then, rats were divided into four subgroups: ND, ND + E, HF and HF + E. The subgroups with + E were given 50 μg/kg estrogen subcutaneously once a day for 30 days. At the end of the experimental period, blood and brain samples were collected to determine the peripheral insulin resistance and neuronal insulin resistance, respectively.Key findingsBoth male and female rats fed with HF developed peripheral insulin resistance as indicated by increased body weight, visceral fat, plasma insulin and HOMA index. Estrogen administration decreased those parameters, indicating improved peripheral insulin sensitivity, in both male and female HF rats. HF diet consumption also caused impaired insulin-induced long-term depression in hippocampus and impaired neuronal insulin receptor function and signaling, indicating neuronal insulin resistance, in both male and female rats. Estrogen treatment could attenuate these neuronal impairments only in HF female rats.SignificanceThe activation of the estrogen pathway could preserve insulin sensitivity in the peripheral tissue in both male and female rats. In neuronal tissue, however, the benefit of estrogen could be found only in female rats.