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Osteoporosis and obesity are prevalent diseases in menopause. The phytoestrogen genistein (Gen) is an antioxidant/anti-inflammatory agent proposed as natural therapy to counteract syndromes associated to menopause. In this work we evaluated the bone effect of Gen in a stress environment induced by hypoestrogenism and obesity. Bilaterally ovariectomized female Wistar rats were fed with high-fat diet (obese), or standard diet (non-obese). Osteoblasts (OB) primary cultures from femoral shafts, and retroperitoneal explants of white adipose tissue (WAT) in vitro exposed to Gen were employed as experimental systems. In obese rats, bone oxidative stress revealed by enhancement on H 2 O 2 release, and significant reduction in OB nitric oxide (NO) production, cell growth, alkaline phosphatase activity (ALP), matrix mineralization and collagen deposition was detected. In OB-WAT co-cultures, Gen treatment inhibited H 2 O 2 secretion, and prompted OB differentiation. A direct action of Gen on WAT was demonstrated. The phytoestrogen inhibited H 2 O 2 and TBARS production, and diminished the secretion of the inflammatory adipokine leptin, through a mechanism of action mediated by estrogen receptor (ER) involvement, and MAPK and PI3K signal transduction pathways participation. A directional interaction from WAT to bone was evidenced by the incubation OB with conditioned medium obtained from WAT exposed to Gen (Gen-CM). The presence of Gen-CM improved OB growth, and reduced H 2 O 2 production. The antioxidative effect of Gen on obese bone cells was partially dependent on its ability to reduce leptin secretion by WAT. Altogether, the results suggest that, under obesity, Gen may improve bone metabolism through a direct action on WAT., Competing Interests: Declaration of competing interest Declarations of interest: none., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The hypothesis whether estrone (E 1 ) could exhibit a direct action at uterus and white adipose tissue (WAT), under obesity was tested. In uterine tissue of obese rats, E 1 increased nitric oxide (NO) synthesis, and reduced reactive oxygen species (ROS) production. The anti-oxidative action of E 1 was sustained under inflammatory stress or high glucose levels. ICI 182780 or G15 compounds were employed as ER or GPER antagonists respectively. The action of E 1 on ROS release involved ER participation; instead GPER mediated the acute stimulation on NO production. The antioxidative effect depends on NO-ROS balance. NO synthase (NOS) blockage suppressed the reduction in ROS synthesis elicited by E 1 , effect mediated by cNOS and not by iNOS. On WAT explants, E 1 reduced ROS and thiobarbituric acid reactive substances production, and diminished leptin release. In summary, the data provide evidence that, in uterus and WAT, E 1 counteracts inflammatory and oxidative stress induced by obesity., Competing Interests: Declaration of competing interest The author(s) declare(s) that there is no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)