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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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Energy Expenditure and Food Intake.Energy expenditure (mL/kg/hr) measured over a 72-hr period by indirect calorimetry. (A) Oxygen consumption and carbon dioxide (CO2) production decline with age, across both sexes and all exposure groups. P-values represent differences from control. (B) Food intake across the life-course, stratified by sex. Stars indicate p-values<0.05 as compared to control. Linear trend p-values represent exposure-dependent trend significance.
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pone-0104273-g002: Energy Expenditure and Food Intake.Energy expenditure (mL/kg/hr) measured over a 72-hr period by indirect calorimetry. (A) Oxygen consumption and carbon dioxide (CO2) production decline with age, across both sexes and all exposure groups. P-values represent differences from control. (B) Food intake across the life-course, stratified by sex. Stars indicate p-values<0.05 as compared to control. Linear trend p-values represent exposure-dependent trend significance.

Mentions: Both sexes showed an age-dependent decline in oxygen consumption (VO) and carbon dioxide (CO2) production (VCO); although females consistently had higher levels of both (Fig. 2a, 2b). Female VO ranged from 4291–5374 mL/kg/hr at 3 months, 3921–4924 mL/kg/hr at 6 months, and 3619–4051 mL/kg/hr at 9 months, whereas the ranges for males were 3796–3919 mL/kg/hr at 3 months, 3413–3527 mL/kg/hr at 6 months, and 2889–3372 mL/kg/hr at 9 months (Fig. 2a). Mean VO levels during the life course differed across exposure groups for females and males (p<0.0001 and p<0.0001, respectively). In females, VO among all exposed groups was at least 500 mL/kg/hr higher relative to controls at the 3-month time point (p = 0.02, p<0.01, p = 0.01 for 2.1 ppm, 16 ppm, and 32 ppm, respectively), but by 6 months of age, only the 32 ppm exposure group had significantly higher VO relative to control (p = 0.01). By 9 months of age VO differences across exposure groups were no longer significant. In contrast, males did not show exposure dependent VO differences until the 9-month time point: the 16 ppm and 32 ppm groups had higher VO relative to control (p = 0.03, p = 0.02, respectively) (Fig. 2a) with the largest of these differences approximately 400 mL/kg/hr.


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)

Energy Expenditure and Food Intake.Energy expenditure (mL/kg/hr) measured over a 72-hr period by indirect calorimetry. (A) Oxygen consumption and carbon dioxide (CO2) production decline with age, across both sexes and all exposure groups. P-values represent differences from control. (B) Food intake across the life-course, stratified by sex. Stars indicate p-values<0.05 as compared to control. Linear trend p-values represent exposure-dependent trend significance.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0104273-g002: Energy Expenditure and Food Intake.Energy expenditure (mL/kg/hr) measured over a 72-hr period by indirect calorimetry. (A) Oxygen consumption and carbon dioxide (CO2) production decline with age, across both sexes and all exposure groups. P-values represent differences from control. (B) Food intake across the life-course, stratified by sex. Stars indicate p-values<0.05 as compared to control. Linear trend p-values represent exposure-dependent trend significance.
Mentions: Both sexes showed an age-dependent decline in oxygen consumption (VO) and carbon dioxide (CO2) production (VCO); although females consistently had higher levels of both (Fig. 2a, 2b). Female VO ranged from 4291–5374 mL/kg/hr at 3 months, 3921–4924 mL/kg/hr at 6 months, and 3619–4051 mL/kg/hr at 9 months, whereas the ranges for males were 3796–3919 mL/kg/hr at 3 months, 3413–3527 mL/kg/hr at 6 months, and 2889–3372 mL/kg/hr at 9 months (Fig. 2a). Mean VO levels during the life course differed across exposure groups for females and males (p<0.0001 and p<0.0001, respectively). In females, VO among all exposed groups was at least 500 mL/kg/hr higher relative to controls at the 3-month time point (p = 0.02, p<0.01, p = 0.01 for 2.1 ppm, 16 ppm, and 32 ppm, respectively), but by 6 months of age, only the 32 ppm exposure group had significantly higher VO relative to control (p = 0.01). By 9 months of age VO differences across exposure groups were no longer significant. In contrast, males did not show exposure dependent VO differences until the 9-month time point: the 16 ppm and 32 ppm groups had higher VO relative to control (p = 0.03, p = 0.02, respectively) (Fig. 2a) with the largest of these differences approximately 400 mL/kg/hr.

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