Participação do relógio biológico no efeito do estradiol sobre o ganho de peso induzido pela ovariectomia

Abstract

Energy balance depends on the functioning of biological clock molecular machinery in such a way that clock-genes-knockout mice are obese. In rats, ovariectomy causes body weight gain, similar effect observed in post-menopausal women. It is known that estrogenic hormonal replacement is capable of reverting this condition. In light of this we hypothesize that estradiol´s role in reducing body weight gain induced by ovariectomy could be via its action over biological clock. We evaluated the effects of cypionate of estradiol injections (E2-injected, 10 µg/0,2mL) and the effects of 17- β- estradiol (17β-E2-Pellet, 180 µg/mL) in sillastic pellets over body-weight changes, white adipose tissue weight and circadian rhythms parameters (rhythm amplitude, spontaneous locomotor activity and core temperature pattern) of ovariectomized (OVX) rats. For spontaneous locomotor activity and core temperature pattern recordings, telemetry sensors were implanted into the animals' abdominal cavities. Besides, we investigated clock genes expression (Per1, Bmal1 and Rev-erbα) in retroperitoneal white adipose tissue (TAR) once this tissue showed a weight reduction after estradiol treatment. Both estradiol treatments were able to reduce body weight gain induced by ovariectomy. After E2-injected administration, Per1 mRNA expression was elevated. Bmal1 expression temporally varied in 17β-E2-Pellet group, with higher levels at ZT0, while E2-Injected animals did not show any difference in Bmal1 mRNA expression. E2 injected treatment also elevated Reverb-α expression. The onset of activity was anticipated after 7 and 10 days of ovariectomy and there was a tendency for a delay in this time after 21 days. Offset and acrophase were not altered after both E2 treatments(injection of cipionato de E2 or 17β-E2-Pellet). Concerning the core temperature, it was observed a statistic difference among intact and OVX rats, the first group showing higher core temperature values at light phase. E2-injected rats showed higher core temperature than Oil-injected rats at dark phase. E2-Pellet and Oil-Pellet groups did not differ statistically in core temperature, but apparently, E2-Pellet rats showed higher core temperature values. The amplitude of core temperature rhythm was reduced after 7 days of ovariectomy and it was higher than the intact rats after 21 days of pellet implantation. In conclusion, the effects of body weight gain reduction caused by E2 treatment can be a result of the action of this hormone over the biological clock synchronization within white adipose tissue (peripheral clock) considering that clock gene expression was altered in this tissue after E2 treatment. Furthermore, estradiol seems to influence on central clock, in the suprachiasmatic nucleus of the hypothalamus, because this hormone changed the circadian rhythm of core temperature.