Abstract
The increasing global prevalence of obesity, exacerbated by factors such as high-fat diets and reduced physical activity, poses a substantial risk for lifestyle-related diseases, particularly in postmenopausal women. Premenopausal women initially have a lower incidence of cardiovascular disease than men, but this risk increases after menopause, highlighting menopause as a critical risk factor. Our previous study showed that the extract of Cordyceps militaris (CM) modulates androgen metabolism partially by inhibiting the gene expression of catabolizing enzyme 5α-reductase. In this study, we investigated the effect of CM on estrogen deficiency-induced obesity in ovariectomized (OVX) mice fed a 0.1% CM diet (estimated human equivalent dose: 7.5 g/day) for 52 days. OVX mice had increased body weight, which subsequently decreased with CM, without altering daily food intake. Regarding visceral fat, CM suppressed OVX-induced adipogenic markers (Pparg, Cebpa, Cebpb, Fabp4, and Adipoq) and protein levels of C/EBPβ, PPARγ, and p-AKT. CM effectively reversed the OVX-induced reduction in the levels of adipose Cyp17a1 and Hsd17b1, key enzymes involved in steroid hormone biosynthesis, increased the cellular senescence markers p21 and p53, and decreased Lmnb1 expression. CM reduced the expression of oxidative stress markers HO-1, NRF2, and 4-HNE. Moreover, CM increased uterine weight and serum superoxide dismutase in 17β-estradiol-treated OVX rats. These findings suggested that CM, particularly its component cordycepin, holds promise as a natural agent for mitigating weight gain, particularly in the context of postmenopausal obesity.