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United States Department of Agriculture

Agricultural Research Service

Research Project: BONE METABOLISM IN OBESITY Title: N-acetylcysteine supplementation decreases osteoclast differentiation and improves bone microstructure in mice fed a high-fat diet

Authors
item Cao, Jay
item Picklo, Matthew

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: December 10, 2013
Publication Date: N/A

Interpretive Summary: Obesity induced by high-fat diets increases bone resorption, decreases trabecular bone mass, and reduces bone strength in various animal models. We investigated whether N-acetylcysteine (NAC), an antioxidant and a glutathione precursor, alters oxidative defense and improves 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 at 1 g/kg diet for 17 wks. We demonstrate that NAC supplementation increased concentrations of serum reduced glutathione, bone volume/total volume, while decreased body weight gain, osteoclast differentiation, and bone structural model index. Osteoclast-like RAW 264.7 cells treated with NAC in vitro had elevated glutathione status and decrease in osteoclast formation. Therefore, NAC can be used to improve bone health in obesity.

Technical Abstract: Studies have demonstrated that obesity induced by high-fat diets increases bone resorption, decreases trabecular bone mass, and reduces bone strength in various animal models. This study investigated whether N-acetylcysteine (NAC), an antioxidant and a glutathione precursor, alters glutathione status and mitigates bone microstructure deterioration 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 at 1 g/kg diet for 17 wks. Compared to the normal-fat group, mice in the high-fat groups had higher body weight, and increased concentrations of serum leptin and oxidized glutathione, osteoclast differentiation, trabecular separation, and structural model index, while had decreased trabecular bone volume, trabecular number, connectivity density, and bone mineral density (P < 0.05). NAC supplementation increased concentrations of serum reduced glutathione, bone volume/total volume, and decreased body weight gain, osteoclast differentiation, and bone structural model index (P < 0.05). Osteoclast-like RAW 264.7 cells treated with NAC in vitro had elevated glutathione status and decreased in osteoclast formation. These results demonstrate that NAC supplementation decreases osteoclast differentiation and is beneficial to bone structure of obese mice induced by a high-fat diet by elevating glutathione status and decreasing bone resorption.

Last Modified: 4/21/2014
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