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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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Weekly Body Weight Measurements.Male offspring across all exposure groups (grams) were weighed. Both medium and high exposure groups are significantly increased in weight across the life course as compared to control mice (in green). Arrows indicate weeks when mice were transferred for physiological parameter testing resulting in stress-induced weight loss. Bars represent 95% confidence intervals. P-values were obtained by adjusting for litter, and the autoregressive structure within mice, and adjusting for week using indicator variables for week of measurement.
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pone-0104273-g003: Weekly Body Weight Measurements.Male offspring across all exposure groups (grams) were weighed. Both medium and high exposure groups are significantly increased in weight across the life course as compared to control mice (in green). Arrows indicate weeks when mice were transferred for physiological parameter testing resulting in stress-induced weight loss. Bars represent 95% confidence intervals. P-values were obtained by adjusting for litter, and the autoregressive structure within mice, and adjusting for week using indicator variables for week of measurement.

Mentions: When measured weekly at the colony housing location, male (p<0.0001) but not female (p = 0.77) mice showed sustained Pb-dependent differences in body weight. Compared to controls, males in the two highest exposure groups were heavier (p<0.001 and p = 0.006 for 16 ppm and 32 ppm, respectively) (Fig. 3). Three transport events to and from the physiological testing facility caused stress-induced fluctuations in weight across all groups, before a return to normal weight gain patterns as indicated by arrows in Figure 3. During the periods when the mice were at the colony housing location, 16 ppm exposed male mice were on average 3.4±1.4 g (p = 0.02) and 3.9±1.4 g (p = 0.01) heavier than control mice during weeks 12–22 and 24–35, respectively; 32 ppm exposed male mice were on average 2.8±1.4 g (p = 0.05) and 3.2±1.4 g (p = 0.02) heavier than control mice during weeks 12–22 and 24–35, respectively. Given the average weight of control male mice during those time periods (35.2±1.7 and 40.1±1.2 g, respectively), these exposure-related differences represent approximately an 8 to 10% increase in body weight. Weights at MNORC time points are given in Table 1.


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)

Weekly Body Weight Measurements.Male offspring across all exposure groups (grams) were weighed. Both medium and high exposure groups are significantly increased in weight across the life course as compared to control mice (in green). Arrows indicate weeks when mice were transferred for physiological parameter testing resulting in stress-induced weight loss. Bars represent 95% confidence intervals. P-values were obtained by adjusting for litter, and the autoregressive structure within mice, and adjusting for week using indicator variables for week of measurement.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0104273-g003: Weekly Body Weight Measurements.Male offspring across all exposure groups (grams) were weighed. Both medium and high exposure groups are significantly increased in weight across the life course as compared to control mice (in green). Arrows indicate weeks when mice were transferred for physiological parameter testing resulting in stress-induced weight loss. Bars represent 95% confidence intervals. P-values were obtained by adjusting for litter, and the autoregressive structure within mice, and adjusting for week using indicator variables for week of measurement.
Mentions: When measured weekly at the colony housing location, male (p<0.0001) but not female (p = 0.77) mice showed sustained Pb-dependent differences in body weight. Compared to controls, males in the two highest exposure groups were heavier (p<0.001 and p = 0.006 for 16 ppm and 32 ppm, respectively) (Fig. 3). Three transport events to and from the physiological testing facility caused stress-induced fluctuations in weight across all groups, before a return to normal weight gain patterns as indicated by arrows in Figure 3. During the periods when the mice were at the colony housing location, 16 ppm exposed male mice were on average 3.4±1.4 g (p = 0.02) and 3.9±1.4 g (p = 0.01) heavier than control mice during weeks 12–22 and 24–35, respectively; 32 ppm exposed male mice were on average 2.8±1.4 g (p = 0.05) and 3.2±1.4 g (p = 0.02) heavier than control mice during weeks 12–22 and 24–35, respectively. Given the average weight of control male mice during those time periods (35.2±1.7 and 40.1±1.2 g, respectively), these exposure-related differences represent approximately an 8 to 10% increase in body weight. Weights at MNORC time points are given in Table 1.

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