Project Number: 5450-51000-046-00
Project Type: Appropriated

Start Date: Apr 09, 2010
End Date: Sep 30, 2014

Objective:
To determine how nutritional, hormonal, and physiological factors affect bone loss/gain in obesity through modifying obesity-induced inflammatory stress. Specifically, we will determine the extent to which obesity is associated with elevated levels of pro-inflammatory cytokines known to promote bone resorption, determine how obesity affects functions of bone cells and bone metabolism, determine the extent to which existing chronic inflammatory stress (induced experimentally by lipopolysaccharide implantation), estrogen deficiency (affected by ovariectomy), and subclinical magnesium intake impair bone health in obese animal models and in obese human subjects, and determine how moderate physical activity preserves bone structure as compared to caloric restriction during weight reduction in an obese animal model.

Approach:
Studies will utilize cell culture, animal models and human subjects. We will use diet-induced obese mice or rats to determine the mechanisms by which adiposity interacts with other dietary, hormonal and physiological factors, such as estrogen deficiency, chronic inflammation, magnesium intake, and moderate exercise, and affects bone structure and functions of osteoblasts and osteoclasts. Human studies will use the in-house Community Studies Unit and the Metabolic Research Unit to conduct supplementation and controlled feeding experiments, respectively. We will determine whether 300 mg/d Mg supplementation to obese postmenopausal women with suspected marginal magnesium deficiency, ameliorates pro-inflammatory cytokine production and improves biomarkers of bone resorption and formation balance.