Physiological profile regulation during weight gain and loss by ovariectomized females: importance of SIRT1 and SIRT4

Obesity in menopausal women occurs because of the systemic effects of loss of ovarian function, resulting in increased body weight and oxidative stress. Caloric restriction (CR) is essential fin - weight loss, since it provides benefits associated with metabolic noimalization resulting from the action of sirtuins. The aim of this work was to evaluate the physiological effects of weight cycling in ovariectomized females. Females aged 2 mo (n = 8/group) were submitted to simulated surgery, ovariectomy (OVX group), and ovariectomy with weight fluctuation (WF group). In the WF group, weight cycling was performed two times, using 21 days of ad libitum commercial feed and 21 days of caloric restriction with 40% of the feed consumed by the OVX group. After 17 wk, the animals were evaluated experimentally. Weight fluctuations reduced triacylglycerol and the adipose tissue index of the WF animals, while increasing the expression of antioxidant proteins. In addition to causing fluctuations in the physiological parameters, the weight cycling led to increases of adipocyte number and serum fatty acids. These effects were reflected in increased expression of the sirtuin (SIRT) 1 and SIRT4 proteins, as well as protein complexes of the mitochondrial electron transport chain, especially in the liver and adipose tissues. The weight-cycling results suggested that mitochondrial and nuclear sirtuins were active in cellular signaling for the control of lipid metabolism, oxidative phosphorylation, and redox status. Weight cycling was able to restore the health characteristics of lean animals.