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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





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Research Project: Health Roles of Dietary Selenium in Obesity Location:
                                Dietary Prevention of Obesity-related Disease Research Title:   Author  item
                                            Yan, Linitem
                                            Nielsen, Forrest

                                                         - *Frosty*item
                                            Sundaram, Snehaitem
                                            Cao, Jay
  Submitted to: Anticancer Research
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 5/7/2015
                                    Publication  Date: 7/1/2015
                                    Publication URL: http://handle.nal.usda.gov/10113/61052Citation: Yan, L., Nielsen, F.H., Sundaram, S., Cao, J.J. 2015. High-fat diet enhances and plasminogen activator inhibitor-1 deficiency attenuates bone loss in mice with Lewis Lung carcinoma. Anticancer Research. 35(7):3839-3847.Interpretive Summary: Cancer spread or metastasis is the most devastating aspect of cancer.  It occurrence is accompanied by wasting, including bone deterioration, continuously throughout the course of malignant progression.  Obesity is a risk factor for cancer, and excessive body fat produces inflammatory factors (for example, plasminogen activator inhibitor-1 (PAI-1)) that contribute to cancer.  We studied the effects of a high-fat diet and PAI-1 deficiency on bone structural changes in mice with cancer metastases in the lungs.  We found bone loss in mice bearing lung metastases, and consumption of a high-fat diet enhanced this bone loss.  However, PAI-1 deficiency attenuated this bone loss.  Our findings indicate that cancer spread is accompanied by bone loss and that obesity, through production of PAI-1, enhances this bone loss.  It suggests that prevention of obesity is important to improve the quality life of cancer survivors by reducing the risk of metastasis-associated bone loss.
                                Technical Abstract: This study determined the effects of a high-fat diet and plasminogen activator inhibitor-1 deficiency (PAI-1-/-) on bone structure in mice bearing Lewis lung carcinoma (LLC) in lungs.  Reduction in bone volume fraction (BV/TV) by 22% and 21%, trabecular number (Tb.N) by 8% and 4% and bone mineral density (BMD) by 17% and 15% in right femurs and vertebrae, respectively, were found in LLC-bearing mice compared to non-tumor-bearing mice (p<0.01 for each comparison).  In LLC-bearing mice, the high-fat diet compared to the AIN93G control diet further reduced BV/TV by 18% , Tb.N by 8% and BMD by 14% in femurs and reduced BV/TV by 9% in vertebrae.  The high-fat diet decreased BMD by 12% in vertebrae in wild-type mice but not in PAI-1-/- mice.  Compared to wild-type mice, PAI-1-/- mice exhibited a 19% increase in BV/TV and a 5% increase in Tb.N in femurs.  The plasma concentration of osteocalcin was 24% lower and TRAP 5b was 80% higher in LLC-bearing mice than in non-tumor-bearing mice.  The high-fat diet compared to the AIN93G diet further decreased plasma osteocalcin by 33% and increased TRAP 5b by 67%.  Deficiency in PAI-1 did not affect plasma concentration of osteocalcin but completely prevented the high-fat diet-induced increase in plasma TRAP 5b in wild-type mice.  These findings indicate that LLC metastasis is accompanied by bone loss.  A high-fat diet enhances this bone loss, however, PAI-1 deficiency attenuates this loss.  It indicates that a high-fat diet and PAI-1 contribute positively to metastasis-associated bone deterioration.


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