Caio Jordão Teixeira1, Luciene Maria Ribeiro1, Katherine Veras2, Layanne Cabral da Cunha Araujo1, Rui Curi3, Carla Roberta de Oliveira Carvalho4. 1. Department of Physiology and Biophysics, Institute of Biomedical Science, University of Sao Paulo, 1524 Prof. Lineu Prestes Ave., ICB 1, Sao Paulo 05508-900, SP, Brazil. 2. Department of Nutrition, University of Mogi das Cruzes, 200 Dr. Cândido X. A. Souza Ave., Sao Paulo 08780-911, SP, Brazil. 3. Interdisciplinary Post-Graduate Program in Health Sciences, Cruzeiro do Sul University, 868 Galvao Bueno, Sao Paulo 01506-000, SP, Brazil. 4. Department of Physiology and Biophysics, Institute of Biomedical Science, University of Sao Paulo, 1524 Prof. Lineu Prestes Ave., ICB 1, Sao Paulo 05508-900, SP, Brazil. Electronic address: croc@icb.usp.br.
Abstract
AIMS: Dehydroepiandrosterone (DHEA) is an adrenal steroid hormone that is a precursor of sexual hormones. It is reduced during aging and is strongly associated with insulin resistance and obesity. There is evidence for beneficial effects of this steroid, in both human and animal models, during perimenopause. However, the impact of DHEA treatment during late postmenopause on glucose metabolism is not clearly documented. We tested the hypothesis that DHEA supplementation could improve insulin sensitivity in an ovariectomized obese rat model (OVX) that was fed a high-fat diet for 11 weeks. MAIN METHODS: Female Wistar rats at 8 weeks of age were OVX or SHAM-operated. Eight weeks after the surgery, the animals were randomly treated with vehicle or DHEA for 3 weeks. Food intake, metabolic parameters and insulin sensitivity were evaluated. KEY FINDINGS: Following the ovariectomy, increased body weight gain, adiposity index, and feeding efficiency were observed, despite there being no change in food and energy intake. The OVX rats also displayed glucose intolerance, insulin resistance, decreased insulin-induced IRS1/2 tyrosine phosphorylation in the skeletal muscle, and reduced serum VLDL-c and TAG levels. OVX rats treated with 10 mg/kg DHEA (OVX + DHEA) exhibited estradiol (E2) serum levels similar to SHAM animals, with no change in uterus mass. DHEA treatment also resulted in an increase in energy intake. SIGNIFICANCE: Despite the positive effects of DHEA supplementation observed in menopausal women and ovariectomized rats, a potential negative effect on glucose metabolism and insulin action in the late postmenopausal condition in diet-induced obese OVX rats are reported.
AIMS: Dehydroepiandrosterone (DHEA) is an adrenal steroid hormone that is a precursor of sexual hormones. It is reduced during aging and is strongly associated with insulin resistance and obesity. There is evidence for beneficial effects of this steroid, in both human and animal models, during perimenopause. However, the impact of DHEA treatment during late postmenopause on glucose metabolism is not clearly documented. We tested the hypothesis that DHEA supplementation could improve insulin sensitivity in an ovariectomized obeserat model (OVX) that was fed a high-fat diet for 11 weeks. MAIN METHODS: Female Wistar rats at 8 weeks of age were OVX or SHAM-operated. Eight weeks after the surgery, the animals were randomly treated with vehicle or DHEA for 3 weeks. Food intake, metabolic parameters and insulin sensitivity were evaluated. KEY FINDINGS: Following the ovariectomy, increased body weight gain, adiposity index, and feeding efficiency were observed, despite there being no change in food and energy intake. The OVX rats also displayed glucose intolerance, insulin resistance, decreased insulin-induced IRS1/2 tyrosine phosphorylation in the skeletal muscle, and reduced serum VLDL-c and TAG levels. OVX rats treated with 10 mg/kg DHEA (OVX + DHEA) exhibited estradiol (E2) serum levels similar to SHAM animals, with no change in uterus mass. DHEA treatment also resulted in an increase in energy intake. SIGNIFICANCE: Despite the positive effects of DHEA supplementation observed in menopausal women and ovariectomized rats, a potential negative effect on glucose metabolism and insulin action in the late postmenopausal condition in diet-induced obese OVX rats are reported.