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Perinatal lead (Pb) exposure results in sex-specific effects on food intake, fat, weight, and insulin response across the murine life-course.

Faulk C, Barks A, Sánchez BN, Zhang Z, Anderson OS, Peterson KE, Dolinoy DC - PLoS ONE (2014)

Bottom Line: Data analyses were stratified by sex and adjusted for litter effects.Exposed females and males exhibited increased energy expenditure as compared to controls (p<0.0001 for both).Overall, food intake increased in exposed females and males (p<0.0008 and p<0.0001, respectively) with significant linear trends at 9 months in females (p = 0.01) and 6 months in males (p<0.01).

View Article: PubMed Central - PubMed

Affiliation: Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, United States of America.

ABSTRACT
Developmental lead (Pb) exposure has been associated with lower body weight in human infants and late onset obesity in mice. We determined the association of perinatal Pb exposure in mice with changes in obesity-related phenotypes into adulthood. Mice underwent exposure via maternal drinking water supplemented with 0 (control), 2.1 (low), 16 (medium), or 32 (high) ppm Pb-acetate two weeks prior to mating through lactation. Offspring were phenotyped at ages 3, 6, and 9 months for energy expenditure, spontaneous activity, food intake, body weight, body composition, and at age 10 months for glucose tolerance. Data analyses were stratified by sex and adjusted for litter effects. Exposed females and males exhibited increased energy expenditure as compared to controls (p<0.0001 for both). In females, horizontal activity differed significantly from controls (p = 0.02) over the life-course. Overall, food intake increased in exposed females and males (p<0.0008 and p<0.0001, respectively) with significant linear trends at 9 months in females (p = 0.01) and 6 months in males (p<0.01). Body weight was significantly increased in males at the medium and high exposures (p = 0.001 and p = 0.006). Total body fat differed among exposed females and males (p<0.0001 and p<0.0001, respectively). Insulin response was significantly increased in medium exposure males (p<0.05). Perinatal Pb exposure at blood lead levels between 4.1 µg/dL and 32 µg/dL is associated with increased food intake, body weight, total body fat, energy expenditure, activity, and insulin response in mice. Physiological effects of developmental Pb exposure persist and vary according to sex and age.

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Lead Exposure Timeline.Dams were exposed 2 weeks prior to mating and throughout pregnancy. Pups continued exposure post-natally during lactation and via direct exposure in drinking water until weaning at day 22. After discontinuation of Pb exposure, mice were assayed for physiological parameters at 3, 6, and 9 months of age at the Michigan Nutrition Obesity Research Center (MNORC), and sacrificed at 10 months of age.
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pone-0104273-g001: Lead Exposure Timeline.Dams were exposed 2 weeks prior to mating and throughout pregnancy. Pups continued exposure post-natally during lactation and via direct exposure in drinking water until weaning at day 22. After discontinuation of Pb exposure, mice were assayed for physiological parameters at 3, 6, and 9 months of age at the Michigan Nutrition Obesity Research Center (MNORC), and sacrificed at 10 months of age.

Mentions: The exposure paradigm consisted of experimentally verified Pb-acetate treated distilled water given ad libitum to dams through weaning (Fig. 1). Mean maternal BLL, tested at weaning, were below the LOD for the control group, and 4.1 (±1.3) µg/dL, 25.1 (±7.3) µg/dL, and 32.1 (±11.4) µg/dL in the three exposure groups, 2.1 ppm, 16 ppm, and 32 ppm, respectively [29]. Average litter size at birth was 7.04 offspring per dam. Although compared to controls, pup survival in the 2.1 ppm group was reduced by 14% at the time of weaning (due to poor maternal care in two litters), there were also no significant differences in litter size at weaning [29]. At weaning there were, on average, 6.41 offspring per dam: control group (n = 11 litters, 78 offspring, with an average of 7.09±0.16 pups per litter); 2.1 ppm group (n = 12 litters, 68 offspring, with an average of 5.6±0.18 pups per litter); 16 ppm group (n = 12 litters, 86 offspring, with an average of 7.17±0.15 pups per litter); 32 ppm group (n = 14 litters, 75 offspring, with an average of 5.35±0.17 pups per litter) [29]. Longitudinal phenotypic measures were taken from a total of 120 a/a mice, on average 2.7 mice per litter (range 1–6 mice from each litter): control (n = 11 litters, 30 offspring); 2.1 ppm group (n = 12 litters, 28 offspring); 16 ppm group (n = 12 litters, 33 offspring); 32 ppm group (n = 14 litters, 29 offspring).


Perinatal lead (Pb) exposure results in sex-specific effects on food intake, fat, weight, and insulin response across the murine life-course.

Faulk C, Barks A, Sánchez BN, Zhang Z, Anderson OS, Peterson KE, Dolinoy DC - PLoS ONE (2014)

Lead Exposure Timeline.Dams were exposed 2 weeks prior to mating and throughout pregnancy. Pups continued exposure post-natally during lactation and via direct exposure in drinking water until weaning at day 22. After discontinuation of Pb exposure, mice were assayed for physiological parameters at 3, 6, and 9 months of age at the Michigan Nutrition Obesity Research Center (MNORC), and sacrificed at 10 months of age.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126699&req=5

pone-0104273-g001: Lead Exposure Timeline.Dams were exposed 2 weeks prior to mating and throughout pregnancy. Pups continued exposure post-natally during lactation and via direct exposure in drinking water until weaning at day 22. After discontinuation of Pb exposure, mice were assayed for physiological parameters at 3, 6, and 9 months of age at the Michigan Nutrition Obesity Research Center (MNORC), and sacrificed at 10 months of age.
Mentions: The exposure paradigm consisted of experimentally verified Pb-acetate treated distilled water given ad libitum to dams through weaning (Fig. 1). Mean maternal BLL, tested at weaning, were below the LOD for the control group, and 4.1 (±1.3) µg/dL, 25.1 (±7.3) µg/dL, and 32.1 (±11.4) µg/dL in the three exposure groups, 2.1 ppm, 16 ppm, and 32 ppm, respectively [29]. Average litter size at birth was 7.04 offspring per dam. Although compared to controls, pup survival in the 2.1 ppm group was reduced by 14% at the time of weaning (due to poor maternal care in two litters), there were also no significant differences in litter size at weaning [29]. At weaning there were, on average, 6.41 offspring per dam: control group (n = 11 litters, 78 offspring, with an average of 7.09±0.16 pups per litter); 2.1 ppm group (n = 12 litters, 68 offspring, with an average of 5.6±0.18 pups per litter); 16 ppm group (n = 12 litters, 86 offspring, with an average of 7.17±0.15 pups per litter); 32 ppm group (n = 14 litters, 75 offspring, with an average of 5.35±0.17 pups per litter) [29]. Longitudinal phenotypic measures were taken from a total of 120 a/a mice, on average 2.7 mice per litter (range 1–6 mice from each litter): control (n = 11 litters, 30 offspring); 2.1 ppm group (n = 12 litters, 28 offspring); 16 ppm group (n = 12 litters, 33 offspring); 32 ppm group (n = 14 litters, 29 offspring).

Bottom Line: Data analyses were stratified by sex and adjusted for litter effects.Exposed females and males exhibited increased energy expenditure as compared to controls (p<0.0001 for both).Overall, food intake increased in exposed females and males (p<0.0008 and p<0.0001, respectively) with significant linear trends at 9 months in females (p = 0.01) and 6 months in males (p<0.01).

View Article: PubMed Central - PubMed

Affiliation: Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, United States of America.

ABSTRACT
Developmental lead (Pb) exposure has been associated with lower body weight in human infants and late onset obesity in mice. We determined the association of perinatal Pb exposure in mice with changes in obesity-related phenotypes into adulthood. Mice underwent exposure via maternal drinking water supplemented with 0 (control), 2.1 (low), 16 (medium), or 32 (high) ppm Pb-acetate two weeks prior to mating through lactation. Offspring were phenotyped at ages 3, 6, and 9 months for energy expenditure, spontaneous activity, food intake, body weight, body composition, and at age 10 months for glucose tolerance. Data analyses were stratified by sex and adjusted for litter effects. Exposed females and males exhibited increased energy expenditure as compared to controls (p<0.0001 for both). In females, horizontal activity differed significantly from controls (p = 0.02) over the life-course. Overall, food intake increased in exposed females and males (p<0.0008 and p<0.0001, respectively) with significant linear trends at 9 months in females (p = 0.01) and 6 months in males (p<0.01). Body weight was significantly increased in males at the medium and high exposures (p = 0.001 and p = 0.006). Total body fat differed among exposed females and males (p<0.0001 and p<0.0001, respectively). Insulin response was significantly increased in medium exposure males (p<0.05). Perinatal Pb exposure at blood lead levels between 4.1 µg/dL and 32 µg/dL is associated with increased food intake, body weight, total body fat, energy expenditure, activity, and insulin response in mice. Physiological effects of developmental Pb exposure persist and vary according to sex and age.

Show MeSH
Related in: MedlinePlus