Limits...
Effects of Combined Exposure to Lead and High-Fat Diet on Bone Quality in Juvenile Male Mice.

Beier EE, Inzana JA, Sheu TJ, Shu L, Puzas JE, Mooney RA - Environ. Health Perspect. (2015)

Bottom Line: Pb and HFD each reduced trabecular bone quality and together had a further detrimental effect on these bone parameters.Mechanical bone properties of strength were depressed in Pb-exposed bones, but HFD had no significant effect.Pb and HFD produced selective deficits in bone accrual that were associated with alterations in progenitor cell activity that may involve reduced Wnt signaling.

View Article: PubMed Central - PubMed

Affiliation: Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, USA.

ABSTRACT

Background: Lead (Pb) exposure and obesity are co-occurring risk factors for decreased bone mass in the young, particularly in low socioeconomic communities.

Objectives: The goal of this study was to determine whether the comorbidities of Pb exposure and high-fat diet-induced obesity amplify skeletal deficits independently associated with each of these risk factors, and to explore associated mechanisms of the observed deficiencies.

Methods: Five-week-old male C57BL/6J mice were placed on low-fat (10% kcal, LFD) or high-fat (60% kcal, HFD) diets for 12 weeks. Mice were exposed to lifetime Pb (50 ppm) through drinking water.

Results: HFD was associated with increased body mass and glucose intolerance. Both HFD and Pb increased fasting glucose and serum leptin levels. Pb and HFD each reduced trabecular bone quality and together had a further detrimental effect on these bone parameters. Mechanical bone properties of strength were depressed in Pb-exposed bones, but HFD had no significant effect. Both Pb and HFD altered progenitor cell differentiation, promoting osteoclastogenesis and increasing adipogenesis while suppressing osteoblastogenesis. In support of this lineage shift being mediated through altered Wnt signaling, Pb and non-esterified fatty acids in MC3T3 cells increased in vitro PPAR-γ activity and inhibited β-catenin activity. Combining Pb and non-esterified fatty acids enhanced these effects.

Conclusions: Pb and HFD produced selective deficits in bone accrual that were associated with alterations in progenitor cell activity that may involve reduced Wnt signaling. This study emphasizes the need to assess toxicants together with other risk factors relevant to human health and disease.

No MeSH data available.


Related in: MedlinePlus

Effects of HFD and Pb (50 ppm) on histologic and serum bone parameters; Pb-exposed and control mice were placed on LFD or HFD for 6 weeks. Serum bone formation marker P1NP (A), resorption marker TRAP5b (B), leptin (C), NEFA (D), sclerostin (E), and DKK1 (F) were measured using ELISA methods. Data are mean ± SEM of 5 mice/group. (G) Trabecular bone in the proximal tibia was assessed histologically by Alcian blue hematoxylin/orange G staining (bar = 100 μm); images are representative sections from treatment groups, selected for approximation to the median BV/TV of its group. Abbreviations: AdV/BV, adipocyte volume/bone volume; Ad size, adipocyte size; BV/TV, bone volume/ total tissue volume; N.Oc/Tb.Ar, number of osteoclasts/trabecular bone area; Oc.S/BS, osteoclast surface/bone surface. The effects of Pb and/or HFD on osteoclast and adipogenic parameters were calculated and are presented at the bottom of each image. Data represent mean ± SEM for 3 mice/group.*p < 0.05 for effect of Pb or diet. #p < 0.05 for interaction of Pb and diet.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4590747&req=5

f3: Effects of HFD and Pb (50 ppm) on histologic and serum bone parameters; Pb-exposed and control mice were placed on LFD or HFD for 6 weeks. Serum bone formation marker P1NP (A), resorption marker TRAP5b (B), leptin (C), NEFA (D), sclerostin (E), and DKK1 (F) were measured using ELISA methods. Data are mean ± SEM of 5 mice/group. (G) Trabecular bone in the proximal tibia was assessed histologically by Alcian blue hematoxylin/orange G staining (bar = 100 μm); images are representative sections from treatment groups, selected for approximation to the median BV/TV of its group. Abbreviations: AdV/BV, adipocyte volume/bone volume; Ad size, adipocyte size; BV/TV, bone volume/ total tissue volume; N.Oc/Tb.Ar, number of osteoclasts/trabecular bone area; Oc.S/BS, osteoclast surface/bone surface. The effects of Pb and/or HFD on osteoclast and adipogenic parameters were calculated and are presented at the bottom of each image. Data represent mean ± SEM for 3 mice/group.*p < 0.05 for effect of Pb or diet. #p < 0.05 for interaction of Pb and diet.

Mentions: Altered bone histomorphometry and serum markers in Pb- and HFD-treated mice. The bone formation marker P1NP was significantly decreased in the HFD group and was further decreased in combination with Pb compared with controls after 6 weeks on diets (Figure 3A). TRAP5b, an indicator of osteoclast number (N.Oc), was elevated in both Pb and HFD groups, but not significantly so. The increase was greater when combined, but the interaction was not significant (Figure 3B). Leptin levels were significantly elevated by both HFD and Pb, but these treatments did not have any interaction (Figure 3C). NEFA were elevated as a consequence of HFD, but Pb had no effect (Figure 3D). The Wnt inhibitors sclerostin (Figure 3E) and DKK1 (Figure 3F) were induced in Pb-exposed mice compared with controls, but HFD antagonized this effect although not significantly.


Effects of Combined Exposure to Lead and High-Fat Diet on Bone Quality in Juvenile Male Mice.

Beier EE, Inzana JA, Sheu TJ, Shu L, Puzas JE, Mooney RA - Environ. Health Perspect. (2015)

Effects of HFD and Pb (50 ppm) on histologic and serum bone parameters; Pb-exposed and control mice were placed on LFD or HFD for 6 weeks. Serum bone formation marker P1NP (A), resorption marker TRAP5b (B), leptin (C), NEFA (D), sclerostin (E), and DKK1 (F) were measured using ELISA methods. Data are mean ± SEM of 5 mice/group. (G) Trabecular bone in the proximal tibia was assessed histologically by Alcian blue hematoxylin/orange G staining (bar = 100 μm); images are representative sections from treatment groups, selected for approximation to the median BV/TV of its group. Abbreviations: AdV/BV, adipocyte volume/bone volume; Ad size, adipocyte size; BV/TV, bone volume/ total tissue volume; N.Oc/Tb.Ar, number of osteoclasts/trabecular bone area; Oc.S/BS, osteoclast surface/bone surface. The effects of Pb and/or HFD on osteoclast and adipogenic parameters were calculated and are presented at the bottom of each image. Data represent mean ± SEM for 3 mice/group.*p < 0.05 for effect of Pb or diet. #p < 0.05 for interaction of Pb and diet.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4590747&req=5

f3: Effects of HFD and Pb (50 ppm) on histologic and serum bone parameters; Pb-exposed and control mice were placed on LFD or HFD for 6 weeks. Serum bone formation marker P1NP (A), resorption marker TRAP5b (B), leptin (C), NEFA (D), sclerostin (E), and DKK1 (F) were measured using ELISA methods. Data are mean ± SEM of 5 mice/group. (G) Trabecular bone in the proximal tibia was assessed histologically by Alcian blue hematoxylin/orange G staining (bar = 100 μm); images are representative sections from treatment groups, selected for approximation to the median BV/TV of its group. Abbreviations: AdV/BV, adipocyte volume/bone volume; Ad size, adipocyte size; BV/TV, bone volume/ total tissue volume; N.Oc/Tb.Ar, number of osteoclasts/trabecular bone area; Oc.S/BS, osteoclast surface/bone surface. The effects of Pb and/or HFD on osteoclast and adipogenic parameters were calculated and are presented at the bottom of each image. Data represent mean ± SEM for 3 mice/group.*p < 0.05 for effect of Pb or diet. #p < 0.05 for interaction of Pb and diet.
Mentions: Altered bone histomorphometry and serum markers in Pb- and HFD-treated mice. The bone formation marker P1NP was significantly decreased in the HFD group and was further decreased in combination with Pb compared with controls after 6 weeks on diets (Figure 3A). TRAP5b, an indicator of osteoclast number (N.Oc), was elevated in both Pb and HFD groups, but not significantly so. The increase was greater when combined, but the interaction was not significant (Figure 3B). Leptin levels were significantly elevated by both HFD and Pb, but these treatments did not have any interaction (Figure 3C). NEFA were elevated as a consequence of HFD, but Pb had no effect (Figure 3D). The Wnt inhibitors sclerostin (Figure 3E) and DKK1 (Figure 3F) were induced in Pb-exposed mice compared with controls, but HFD antagonized this effect although not significantly.

Bottom Line: Pb and HFD each reduced trabecular bone quality and together had a further detrimental effect on these bone parameters.Mechanical bone properties of strength were depressed in Pb-exposed bones, but HFD had no significant effect.Pb and HFD produced selective deficits in bone accrual that were associated with alterations in progenitor cell activity that may involve reduced Wnt signaling.

View Article: PubMed Central - PubMed

Affiliation: Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, USA.

ABSTRACT

Background: Lead (Pb) exposure and obesity are co-occurring risk factors for decreased bone mass in the young, particularly in low socioeconomic communities.

Objectives: The goal of this study was to determine whether the comorbidities of Pb exposure and high-fat diet-induced obesity amplify skeletal deficits independently associated with each of these risk factors, and to explore associated mechanisms of the observed deficiencies.

Methods: Five-week-old male C57BL/6J mice were placed on low-fat (10% kcal, LFD) or high-fat (60% kcal, HFD) diets for 12 weeks. Mice were exposed to lifetime Pb (50 ppm) through drinking water.

Results: HFD was associated with increased body mass and glucose intolerance. Both HFD and Pb increased fasting glucose and serum leptin levels. Pb and HFD each reduced trabecular bone quality and together had a further detrimental effect on these bone parameters. Mechanical bone properties of strength were depressed in Pb-exposed bones, but HFD had no significant effect. Both Pb and HFD altered progenitor cell differentiation, promoting osteoclastogenesis and increasing adipogenesis while suppressing osteoblastogenesis. In support of this lineage shift being mediated through altered Wnt signaling, Pb and non-esterified fatty acids in MC3T3 cells increased in vitro PPAR-γ activity and inhibited β-catenin activity. Combining Pb and non-esterified fatty acids enhanced these effects.

Conclusions: Pb and HFD produced selective deficits in bone accrual that were associated with alterations in progenitor cell activity that may involve reduced Wnt signaling. This study emphasizes the need to assess toxicants together with other risk factors relevant to human health and disease.

No MeSH data available.


Related in: MedlinePlus