title: High-fat Diet Enhances and Plasminogen Activator Inhibitor-1 Deficiency Attenuates Bone Loss in Mice with Lewis Lung Carcinoma.
abstract: This study determined the effects of a high-fat diet and plasminogen activator inhibitor-1 deficiency (Pai1(-/-)) on the bone structure in male C57BL/6 mice bearing Lewis lung carcinoma (LLC) in lungs. Significant reduction in bone volume fraction (BV/TV), trabecular number (Tb.N) and bone mineral density (BMD) in femurs and vertebrae were found in LLC-bearing mice compared to non-tumor-bearing mice. In LLC-bearing mice, the high-fat diet compared to the AIN93G control diet significantly reduced BV/TV, Tb.N and BMD in femurs and BV/TV in vertebrae. The high-fat diet significantly reduced BMD in vertebrae in wild-type mice but not in Pai1(-/-) mice. Compared to wild-type mice, PAI1 deficiency significantly increased BV/TV and Tb.N in femurs. The plasma concentration of osteocalcin was significantly lower and that of tartrate-resistant acid phosphatase 5b (TRAP5b) was significantly higher in LLC-bearing mice. The high-fat diet significantly reduced plasma osteocalcin and increased TRAP5b. Deficiency in PAI1 prevented the high-fat diet-induced increases in plasma TRAP5b. These findings demonstrate that a high-fat diet enhances, whereas PAI1 deficiency, attenuates metastasis-associated bone loss, indicating that a high-fat diet and PAI1 contribute to metastasis-associated bone deterioration.
authors.affiliation: Grand Forks Human Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture, Grand Forks, ND, U.S.A. lin.yan@ars.usda.gov.
authors.forename: Lin
authors.initials: L
authors.lastname: Yan
authors.affiliation: Grand Forks Human Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture, Grand Forks, ND, U.S.A.
authors.forename: Forrest H
authors.initials: FH
authors.lastname: Nielsen
authors.affiliation: Grand Forks Human Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture, Grand Forks, ND, U.S.A.
authors.forename: Sneha
authors.initials: S
authors.lastname: Sundaram
authors.affiliation: Grand Forks Human Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture, Grand Forks, ND, U.S.A.
authors.forename: Jay
authors.initials: J
authors.lastname: Cao
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D015519:Bone Density / Q000502:physiology*; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology*; D018827:Carcinoma, Lewis Lung / Q000378:metabolism / Q000473:pathology*; D059305:Diet, High-Fat / Q000009:adverse effects*; D006474:Hemorrhagic Disorders / Q000378:metabolism / Q000473:pathology*; D007527:Isoenzymes / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015675:Osteocalcin / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000172:deficiency* / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D007527:Isoenzymes; D017395:Plasminogen Activator Inhibitor 1; D015675:Osteocalcin; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase
keywords: High-fat diet; PAI1; bone; metastasis; mice