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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

Effect of dietary fat and Pb (50 ppm) on body weight and glucose in male mice placed on HFD or LFD for 12 weeks. (A) Weight gain of mice recorded over the course of the experiment. (B) Body fat composition in the trunk and legs of mice at 12 weeks by DXA scans. (C) Fasting glucose levels analyzed at the start of the glucose tolerance test. (D) Blood glucose levels measured over time after an intraperitoneal injection of glucose (left); area under the curve analysis shows significant differences between LFD and HFD (right). Data are mean ± SEM of 5 mice/group.*p < 0.05 for effect of Pb or diet. #p < 0.05 for interaction of Pb and diet.
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f1: Effect of dietary fat and Pb (50 ppm) on body weight and glucose in male mice placed on HFD or LFD for 12 weeks. (A) Weight gain of mice recorded over the course of the experiment. (B) Body fat composition in the trunk and legs of mice at 12 weeks by DXA scans. (C) Fasting glucose levels analyzed at the start of the glucose tolerance test. (D) Blood glucose levels measured over time after an intraperitoneal injection of glucose (left); area under the curve analysis shows significant differences between LFD and HFD (right). Data are mean ± SEM of 5 mice/group.*p < 0.05 for effect of Pb or diet. #p < 0.05 for interaction of Pb and diet.

Mentions: Effects of HFD and Pb exposure on glucose levels in growing male mice. To investigate the mechanism of Pb- and obesity-induced bone loss, we exposed male C57BL/6J mice to normal or Pb-treated drinking water beginning at birth. The average blood Pb level in treated mice was 8 μg/dL at 5 weeks of age and 4 μg/dL at 17 weeks of age. Diet had no effect on blood Pb levels. Note that a 5-μg/dL blood Pb level places a child in the top 2.5% of tested children (CDC 2012). When mice were 5 weeks of age [equivalent to 10-year-old children (Grounds et al. 2008)], they were placed on an LFD or HFD. Mice on the HFD gained more weight than LFD mice within 6 weeks, but Pb exposure had no effect on weight (Figure 1A). Fat composition was significantly higher in the trunk and legs of HFD mice compared with controls (Figure 1B). Pb exposure had no effect on fat composition.


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)

Effect of dietary fat and Pb (50 ppm) on body weight and glucose in male mice placed on HFD or LFD for 12 weeks. (A) Weight gain of mice recorded over the course of the experiment. (B) Body fat composition in the trunk and legs of mice at 12 weeks by DXA scans. (C) Fasting glucose levels analyzed at the start of the glucose tolerance test. (D) Blood glucose levels measured over time after an intraperitoneal injection of glucose (left); area under the curve analysis shows significant differences between LFD and HFD (right). Data are mean ± SEM of 5 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

f1: Effect of dietary fat and Pb (50 ppm) on body weight and glucose in male mice placed on HFD or LFD for 12 weeks. (A) Weight gain of mice recorded over the course of the experiment. (B) Body fat composition in the trunk and legs of mice at 12 weeks by DXA scans. (C) Fasting glucose levels analyzed at the start of the glucose tolerance test. (D) Blood glucose levels measured over time after an intraperitoneal injection of glucose (left); area under the curve analysis shows significant differences between LFD and HFD (right). Data are mean ± SEM of 5 mice/group.*p < 0.05 for effect of Pb or diet. #p < 0.05 for interaction of Pb and diet.
Mentions: Effects of HFD and Pb exposure on glucose levels in growing male mice. To investigate the mechanism of Pb- and obesity-induced bone loss, we exposed male C57BL/6J mice to normal or Pb-treated drinking water beginning at birth. The average blood Pb level in treated mice was 8 μg/dL at 5 weeks of age and 4 μg/dL at 17 weeks of age. Diet had no effect on blood Pb levels. Note that a 5-μg/dL blood Pb level places a child in the top 2.5% of tested children (CDC 2012). When mice were 5 weeks of age [equivalent to 10-year-old children (Grounds et al. 2008)], they were placed on an LFD or HFD. Mice on the HFD gained more weight than LFD mice within 6 weeks, but Pb exposure had no effect on weight (Figure 1A). Fat composition was significantly higher in the trunk and legs of HFD mice compared with controls (Figure 1B). Pb exposure had no effect on fat composition.

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