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ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Dietary Prevention of Obesity-related Disease Research » Research » Publications at this Location » Publication #323352
Research Project: Health Roles of Dietary Selenium in Obesity

Location: Dietary Prevention of Obesity-related Disease Research

Title: High-fat diet enhances and monocyte chemoattractant protein-1 deficiency reduces bone loss in mice with pulmonary metastases of Lewis lung carcinoma

Author
item Sundaram, Sneha
item Yan, Lin

Submitted to: American Association of Cancer Research
Publication Type: Abstract Only
Publication Acceptance Date: 5/22/2016
Publication Date: 7/22/2016
Citation: Sundaram, S., Yan, L. 2016. High-fat diet enhances and monocyte chemoattractant protein-1 deficiency reduces bone loss in mice with pulmonary metastases of Lewis lung carcinoma [abstract]. 2016 Annual Meeting of the American Association of Cancer Research, New Orleans, Louisiana, April 16-20, 2016. 76(14):4325.

Interpretive Summary: Bone is adversely affected by metastasis and metastasis-associated complications. Obesity is a risk factor for both bone and cancer. Adipose tissue is an endocrine organ that produces pro-inflammatory adipokines, such as monocyte chemotactic protein-1 (MCP-1), that contribute to obesity and obesity-related diseases. This study (2x2 factorial design) investigated the effects of a high-fat diet (45% of energy from corn oil) and MCP-1 deficiency on bone micro-structural changes, analyzed by micro-computed tomography, in male C57BL/6 mice bearing lung metastases of Lewis lung carcinoma (LLC). Subcutaneous injection of LLC cells resulted in lung metastasis which was significantly enhanced by the high-fat diet and attenuated by MCP-1 deficiency. Micro-computed tomographic measurement showed significant reductions in bone volume fraction (BV/TV), trabecular number (Tb.N) and bone mineral density (BMD) in right femurs and vertebrae of LLC-bearing mice compared to non-tumor-bearing controls. In LLC-bearing mice, compared to the low-fat diet (16% of energy from corn oil), the high-fat diet significantly reduced BV/TV, Tb.N and BMD in femurs but not in vertebrae. Furthermore, compared to wild-type mice, MCP-1 deficiency significantly increased BV/TV and Tb.N in both femurs and vertebrae and BMD in vertebrae in LLC-bearing mice. These results demonstrate that metastasis causes bone loss which is enhanced by the high-fat diet and attenuated by MCP-1 deficiency. Overall, it indicates that the high-fat diet and MCP-1 contribute positively to metastasis-associated bone deterioration.

Technical Abstract: Bone is adversely affected by metastasis and metastasis-associated complications. Obesity is a risk factor for both bone and cancer. Adipose tissue is an endocrine organ that produces pro-inflammatory adipokines, such as monocyte chemotactic protein-1 (MCP-1), that contribute to obesity and obesity-related diseases. This study (2x2 factorial design) investigated the effects of a high-fat diet (45% of energy from corn oil) and MCP-1 deficiency on bone micro-structural changes, analyzed by micro-computed tomography, in male C57BL/6 mice bearing lung metastases of Lewis lung carcinoma (LLC). Subcutaneous injection of LLC cells resulted in lung metastasis which was significantly enhanced by the high-fat diet and attenuated by MCP-1 deficiency. Micro-computed tomographic measurement showed significant reductions in bone volume fraction (BV/TV), trabecular number (Tb.N) and bone mineral density (BMD) in right femurs and vertebrae of LLC-bearing mice compared to non-tumor-bearing controls. In LLC-bearing mice, compared to the low-fat diet (16% of energy from corn oil), the high-fat diet significantly reduced BV/TV, Tb.N and BMD in femurs but not in vertebrae. Furthermore, compared to wild-type mice, MCP-1 deficiency significantly increased BV/TV and Tb.N in both femurs and vertebrae and BMD in vertebrae in LLC-bearing mice. These results demonstrate that metastasis causes bone loss which is enhanced by the high-fat diet and attenuated by MCP-1 deficiency. Overall, it indicates that the high-fat diet and MCP-1 contribute positively to metastasis-associated bone deterioration.