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Effects of a high-fat diet on spontaneous metastasis of Lewis lung carcinoma in plasminogen activator inhibitor-1 deficient and wild-type mice.

Yan L, DeMars LC - PLoS ONE (2014)

Bottom Line: Deficiency in PAI-1 reduced the number of metastases by 35% (p<0.01) compared to wild-type mice.Mice deficient in PAI-1 showed significantly greater plasma concentrations of monocyte chemotactic protein-1, tumor necrosis factor-α, leptin, vascular endothelial growth factor, tissue inhibitor of metalloproteinase-1 and insulin compared to wild-type mice, indicating a compensatory overproduction of inflammatory cytokines, angiogenic factors and insulin in the absence of PAI-1.We conclude that PAI-1 produced by the host, including that by adipose tissue, promotes high-fat enhanced metastasis of LLC.

View Article: PubMed Central - PubMed

Affiliation: Grand Forks Human Nutrition Research Center, United States Department of Agriculture, Agricultural Research Service, Grand Forks, North Dakota, United States of America.

ABSTRACT
This study investigated the effects of a high-fat diet on spontaneous metastasis of Lewis lung carcinoma (LLC) in plasminogen activator inhibitor-1 deficient (PAI-1-/-) and wild-type mice. The high-fat diet increased the number of pulmonary metastases by 60% (p<0.01), tumor cross-sectional area by 82% (p<0.05) and tumor volume by 130% (p<0.05) compared to the AIN93G diet. Deficiency in PAI-1 reduced the number of metastases by 35% (p<0.01) compared to wild-type mice. In mice fed the high-fat diet, PAI-1 deficiency reduced tumor cross-sectional area by 52% (p<0.05) and tumor volume by 61% (p<0.05) compared to their wild-type counterparts; however, PAI-1 deficiency affected neither area nor volume in mice fed the AIN93G diet. Adipose and plasma concentrations of PAI-1 were significantly higher in high-fat fed wild-type mice than in their AIN93G-fed counterparts. Adipose and plasma PAI-1 were not detectable in PAI-1-/- mice regardless of the diet. Mice deficient in PAI-1 showed significantly greater plasma concentrations of monocyte chemotactic protein-1, tumor necrosis factor-α, leptin, vascular endothelial growth factor, tissue inhibitor of metalloproteinase-1 and insulin compared to wild-type mice, indicating a compensatory overproduction of inflammatory cytokines, angiogenic factors and insulin in the absence of PAI-1. We conclude that PAI-1 produced by the host, including that by adipose tissue, promotes high-fat enhanced metastasis of LLC.

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Body weight.Two-way ANOVA and Tukey contrasts were performed to test for differences among the groups. The high-fat diet, compared to the AIN93G diet, increased body weights; the difference was significant starting 4 weeks after the initiation of experimental feeding (p<0.01), and the significant increase continued throughout the experiment. Compared to wild-type mice, PAI-1 deficiency lowered body weights, and the difference was significant starting at week 6 of the experiment (p≤0.05). Values are means ± SEM (n = 11 per group for PAI-1−/− mice, n = 14 per group for wild-type mice; second cohort). AIN WT: AIN93G-fed wild-type mice, AIN PAI-1−/−: AIN93G-fed PAI-1−/− mice, HF WT: high-fat fed wild-type mice, HF PAI-1−/−: high-fat fed PAI-1−/− mice.
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pone-0110869-g001: Body weight.Two-way ANOVA and Tukey contrasts were performed to test for differences among the groups. The high-fat diet, compared to the AIN93G diet, increased body weights; the difference was significant starting 4 weeks after the initiation of experimental feeding (p<0.01), and the significant increase continued throughout the experiment. Compared to wild-type mice, PAI-1 deficiency lowered body weights, and the difference was significant starting at week 6 of the experiment (p≤0.05). Values are means ± SEM (n = 11 per group for PAI-1−/− mice, n = 14 per group for wild-type mice; second cohort). AIN WT: AIN93G-fed wild-type mice, AIN PAI-1−/−: AIN93G-fed PAI-1−/− mice, HF WT: high-fat fed wild-type mice, HF PAI-1−/−: high-fat fed PAI-1−/− mice.

Mentions: Consumption of the high-fat diet increased body weights compared to the AIN93G diet. The difference was statistically significant 4 weeks after the initiation of experimental feeding (high-fat vs. AIN93G: p<0.01), and the significant increase continued throughout the experiment (Fig. 1). Starting at week 6, PAI-1−/− mice weighed significantly less than wild-type mice (PAI-1−/− vs. wild-type: p<0.05, Fig. 1), a difference more marked in the high-fat fed mice. Compared to the AIN93G diet, high-fat diet consumption increased body fat mass by 43% (high-fat vs. AIN93G: p<0.01) with a concomitant reduction in body lean mass by 9% (p<0.01) (Table 2). Compared to wild-type mice, PAI-1−/− mice had a 15% reduction in fat mass (PAI-1−/− vs. wild-type: p<0.01) and a 5% increase in lean mass (p<0.01) (Table 2). Neither the high-fat diet nor PAI-1 deficiency affected absolute lean mass weight (Table 2). Consumption of the high-fat diet increased caloric intake by 8% (high-fat vs. AIN93G: p<0.05) and PAI-1 deficiency lowered caloric intake by 9% (PAI-1−/− vs. wild-type: p<0.05) compared to their respective controls (Table 2).


Effects of a high-fat diet on spontaneous metastasis of Lewis lung carcinoma in plasminogen activator inhibitor-1 deficient and wild-type mice.

Yan L, DeMars LC - PLoS ONE (2014)

Body weight.Two-way ANOVA and Tukey contrasts were performed to test for differences among the groups. The high-fat diet, compared to the AIN93G diet, increased body weights; the difference was significant starting 4 weeks after the initiation of experimental feeding (p<0.01), and the significant increase continued throughout the experiment. Compared to wild-type mice, PAI-1 deficiency lowered body weights, and the difference was significant starting at week 6 of the experiment (p≤0.05). Values are means ± SEM (n = 11 per group for PAI-1−/− mice, n = 14 per group for wild-type mice; second cohort). AIN WT: AIN93G-fed wild-type mice, AIN PAI-1−/−: AIN93G-fed PAI-1−/− mice, HF WT: high-fat fed wild-type mice, HF PAI-1−/−: high-fat fed PAI-1−/− mice.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4214820&req=5

pone-0110869-g001: Body weight.Two-way ANOVA and Tukey contrasts were performed to test for differences among the groups. The high-fat diet, compared to the AIN93G diet, increased body weights; the difference was significant starting 4 weeks after the initiation of experimental feeding (p<0.01), and the significant increase continued throughout the experiment. Compared to wild-type mice, PAI-1 deficiency lowered body weights, and the difference was significant starting at week 6 of the experiment (p≤0.05). Values are means ± SEM (n = 11 per group for PAI-1−/− mice, n = 14 per group for wild-type mice; second cohort). AIN WT: AIN93G-fed wild-type mice, AIN PAI-1−/−: AIN93G-fed PAI-1−/− mice, HF WT: high-fat fed wild-type mice, HF PAI-1−/−: high-fat fed PAI-1−/− mice.
Mentions: Consumption of the high-fat diet increased body weights compared to the AIN93G diet. The difference was statistically significant 4 weeks after the initiation of experimental feeding (high-fat vs. AIN93G: p<0.01), and the significant increase continued throughout the experiment (Fig. 1). Starting at week 6, PAI-1−/− mice weighed significantly less than wild-type mice (PAI-1−/− vs. wild-type: p<0.05, Fig. 1), a difference more marked in the high-fat fed mice. Compared to the AIN93G diet, high-fat diet consumption increased body fat mass by 43% (high-fat vs. AIN93G: p<0.01) with a concomitant reduction in body lean mass by 9% (p<0.01) (Table 2). Compared to wild-type mice, PAI-1−/− mice had a 15% reduction in fat mass (PAI-1−/− vs. wild-type: p<0.01) and a 5% increase in lean mass (p<0.01) (Table 2). Neither the high-fat diet nor PAI-1 deficiency affected absolute lean mass weight (Table 2). Consumption of the high-fat diet increased caloric intake by 8% (high-fat vs. AIN93G: p<0.05) and PAI-1 deficiency lowered caloric intake by 9% (PAI-1−/− vs. wild-type: p<0.05) compared to their respective controls (Table 2).

Bottom Line: Deficiency in PAI-1 reduced the number of metastases by 35% (p<0.01) compared to wild-type mice.Mice deficient in PAI-1 showed significantly greater plasma concentrations of monocyte chemotactic protein-1, tumor necrosis factor-α, leptin, vascular endothelial growth factor, tissue inhibitor of metalloproteinase-1 and insulin compared to wild-type mice, indicating a compensatory overproduction of inflammatory cytokines, angiogenic factors and insulin in the absence of PAI-1.We conclude that PAI-1 produced by the host, including that by adipose tissue, promotes high-fat enhanced metastasis of LLC.

View Article: PubMed Central - PubMed

Affiliation: Grand Forks Human Nutrition Research Center, United States Department of Agriculture, Agricultural Research Service, Grand Forks, North Dakota, United States of America.

ABSTRACT
This study investigated the effects of a high-fat diet on spontaneous metastasis of Lewis lung carcinoma (LLC) in plasminogen activator inhibitor-1 deficient (PAI-1-/-) and wild-type mice. The high-fat diet increased the number of pulmonary metastases by 60% (p<0.01), tumor cross-sectional area by 82% (p<0.05) and tumor volume by 130% (p<0.05) compared to the AIN93G diet. Deficiency in PAI-1 reduced the number of metastases by 35% (p<0.01) compared to wild-type mice. In mice fed the high-fat diet, PAI-1 deficiency reduced tumor cross-sectional area by 52% (p<0.05) and tumor volume by 61% (p<0.05) compared to their wild-type counterparts; however, PAI-1 deficiency affected neither area nor volume in mice fed the AIN93G diet. Adipose and plasma concentrations of PAI-1 were significantly higher in high-fat fed wild-type mice than in their AIN93G-fed counterparts. Adipose and plasma PAI-1 were not detectable in PAI-1-/- mice regardless of the diet. Mice deficient in PAI-1 showed significantly greater plasma concentrations of monocyte chemotactic protein-1, tumor necrosis factor-α, leptin, vascular endothelial growth factor, tissue inhibitor of metalloproteinase-1 and insulin compared to wild-type mice, indicating a compensatory overproduction of inflammatory cytokines, angiogenic factors and insulin in the absence of PAI-1. We conclude that PAI-1 produced by the host, including that by adipose tissue, promotes high-fat enhanced metastasis of LLC.

Show MeSH
Related in: MedlinePlus