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Estrogenic phytochemicals reduce bone adiposity and improves bone quality following ovariectomy.
Citation:
Miller, C., S. Ambati, N. Hohos, D. Hartzell, E. Bass, E. England, T. Avra, M. Della-Fera, C. Baile, AND S. Rayalam. Estrogenic phytochemicals reduce bone adiposity and improves bone quality following ovariectomy. Cardiovascular, Renal and Metabolic Diseases: Physiology and Gender, Annapolis, MD, November 17 - 20, 2015.
Impact/Purpose:
The purpose of the current research was to combine multiple natural products with synergistic activity as a result of actions on multiple molecular targets that impact the life cycle of adipocytes and bone precursor cells which may improve maladaptive body composition changes in a rodent model of menopause.
Description:
Menopause causes increased adiposity and the risk of osteoporosis. Partly as a result of the carcinogenic concerns of hormone replacement therapy, increasing numbers of post-menopausal women are taking botanical and dietary supplements to manage these adverse body composition changes. Adipocytes and osteoblasts share a common progenitor cell, the mesenchymal stem cell, and thus botanical supplements may improve both adipose tissue and bone together. The efficacy of such supplements are often in question, which may be related to the “one molecule, one target” approach. Thus, the goal of the current research was to combine multiple natural products with synergistic activity as a result of actions on multiple molecular targets that impact the life cycle of adipocytes and bone precursor cells. Aged, ovariectomized (OVX) Fisher 344 rats from the National Institute of Aging colony were fed either a control diet or one containing various doses of phytochemicals (diet 1: 1000 mg/kg genistein, (G); diet 2: 500 mg/kg G, 200 mg/kg resveratrol (R), and 1000 mg/kg quercetin (Q); diet 3: 1000 mg/kg G, 400 mg/kg R, and 2000 mg/kg Q). Following 16 weeks, a dose-response in the number of adipocytes was found within femoral trabecular bone; diet 3 in particular caused a significant reduction compared to OVX controls (p<0.01). Bone adiposity was also found to be significantly correlated with the retroperitoneal fat depot, which was additionally reduced with dietary phytochemicals (p<0.05). Bone quality was determined using micro CT measures of the femoral bone. To be expected, OVX reduced bone quality compared to sham rats. Phytochemical supplementation improved trabecular bone quality compared to OVX, however did not completely restore it to levels of sham rats. Serum IGF-1, a bone-promoting hormone, was similarly reduced following OVX. Dietary phytochemicals (diets 1 and 3) improved IGF-1 levels compared to OVX-control rats. While we were unable to completely reverse the damage caused by surgical menopause, the phytochemicals used in our study improved trabecular bone quality and adiposity compared to OVX. Thus we conclude that synergistic, plant-derived compounds with estrogenic properties may be helpful as part of a combined effort to prevent maladaptive bone changes including adipocyte infiltration and structural loss as a result of menopause. Further, we provide mounting evidence that dietary phytochemicals may reduce adiposity as a result of sex hormone deficiency.