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United States Department of Agriculture

Agricultural Research Service

Research Project: Bone Metabolism in Obesity
2013 Annual Report


1a.Objectives (from AD-416):
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.


1b.Approach (from AD-416):
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.


3.Progress Report:
A human study was completed to determine optimal protein intake and musculoskeletal response to energy deficit. Thirty-nine physically active volunteers aged 18 – 42 were recruited to participate in a 31-d live-in, controlled feeding study. Subjects were randomly assigned to three dietary groups: high protein (2.4 g/kg/d), moderate protein (1.6 g/kg/d), or low protein (0.8 g/kg/d). Markers of bone turnover were assessed. Calcium absorption was determined using stable isotope methodology. Muscle biopsies, and various molecular techniques, direct measures of muscle protein synthesis, protein breakdown, and the cellular mechanisms that regulate these processes were also assessed following energy sufficient and insufficient diets. Samples have been analyzed and data have been summarized and submitted for publication.

A study was conducted with cells and animals to determine whether supplementation of N-acetylcysteine, an antioxidant, affects osteoclast formation and mitigates deterioration of bone microstructure in mice fed a high-fat diet. Forty-eight 6-wk-old male C57BL/6 mice were randomly assigned to four treatment groups (n=12/group) and fed either a normal-fat (10% energy as fat) or a high-fat (45% energy as fat) diet ad libitum with or without N-acetylcysteine supplementation (1 g/kg diet) for 17 wks. Changes in osteoclast number in vitro, bone structure, and other serum markers related to bone metabolism were measured.


4.Accomplishments
1. Short-term weight loss by diet and exercise while eating a high-protein diet does not compromise bone health. ARS scientists at Grand Forks, ND, in collaboration with US Army scientists conducted a 31-d live-in, controlled feeding study to determine whether bone metabolism is affected by a high protein diet during weight loss. Data demonstrated that consuming dietary protein at levels above the RDA did not significantly alter bone metabolism. These results will enhance the understanding of the role of high-protein intake in the maintenance of bone heath. The findings can be used by the Dietary Guidelines for Americans (DGA) as the evidence in supporting the use of high-protein diets during periods of weight loss to prevent muscle loss without harming bone metabolism.


Review Publications
Nielsen, F.H. 2012. Calcium, magnesium, and potassium in food. In: Sulewski, G., editor. Fertilizing Crops to Improve Human Health: A Scientific Review. 1st edition. Norcross, GA: International Plant Nutrition Institute, p. 123-142.

Zhu, L., Cao, J.J., Sun, M., Yuen, T., Zhou, R., Li, J., Peng, Y., Moonga, S.S., Guo, L., Mechanick, J.I., Iqbal, J., Peng, L., Blair, H.C., Biam, Z., Zaidi, M. 2012. Vitamin C reverses hypogonadal bone loss. PLoS One. 7(10):1-6.

Nielsen, F.H. 2012. History of zinc in agriculture. Advances in Nutrition. 3:783-789.

Baliram, R., Sun, L., Cao, J.J., Li, J., Latif, R., Huber, A.K., Yuen, T., Blair, H.C., Zaidi, M., Davies, T.F. 2012. Hyperthyroid-associated osteoporosis is exacerbated by the loss of TSH signaling. Journal of Clinical Investigation. 122(10):3737-3741.

Shen, C., Cao, J.J., Dagda, R., Chanjaplammootil, S., Lu, C., Chyu, M., Gao, W., Wang, J., Yeh, J.K. 2012. Green tea polyphenols benefits body composition and improves bone quality in long-term high-fat diet-induced obese rats. Nutrition Research. 32:448-457.

Yan, C., Wu, M., Cao, J.J., Tang, H., Zhu, M., Johnson, P.E., Gao, H. 2012. Critical role for CCAAT/Enhancer-binding protein beta in immune complex-induced acute lung injury. Journal of Immunology. 189(3):1480-90.

Zhu, L., Blair, H.C., Cao, J.J., Yuen, T., Latif, R., Guo, L., Tourkova, I.L., Li, J., Davies, T.F., Sun, L., Bian, Z., Rosen, C., Zallone, A., New, M.I., Zaidi, M. 2012. Blocking antibody to the beta-subunit of FSH prevents bone loss by inhibiting bone resorption and stimulating bone synthesis. Proceedings of the National Academy of Sciences. 109(36):14574-14579.

Colaianni, G., Sun, L., Di Benedetto, A., Tamma, R., Zhu, L., Cao, J.J., Grano, M., Yuan, T., Colucci, S., Cuscito, C., Mancini, L., Li, J., Nishimori, K., Bab, I., Lee, H., Iqbal, J., Young, W., Rosen, C., Zallone, A., Zaidi, M. 2012. Bone marrow oxytocin mediates the anabolic action of estrogen on the skeleton. Proceedings of the National Academy of Sciences. 287(34):29159-29167.

Pasiakos, S.M., Cao, J.J., Margolis, L.M., Sauter, E.R., Whigham Grendell, L.D., Mcclung, J.P., Rood, J.C., Carbone, J.W., Combs, G.F., Young, A.J. 2013. Effects of high protein diets on fat-free mass and muscle protein synthesis following weight loss: a randomized controlled trial. Journal of Federation of American Societies for Experimental Biology. doi: 10.1096/fj.13-230227.

Last Modified: 4/18/2014
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