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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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Blood Insulin and Glucose (9 months).(A) Glucose (mg/dl) measured by a fasting oral glucose tolerance AUC did not differ in either males or females. (B) Insulin (ng/ml) is increased in males at the medium exposure area under the curve (AUC) and (C) Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Calculated from baseline blood insulin and glucose levels, indicates an index of insulin resistance. Males at the medium exposure level show a significant increase in HOMA-IR as over control. Single stars indicate p-values<0.05, when compared to controls. Bars represent standard error.
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pone-0104273-g005: Blood Insulin and Glucose (9 months).(A) Glucose (mg/dl) measured by a fasting oral glucose tolerance AUC did not differ in either males or females. (B) Insulin (ng/ml) is increased in males at the medium exposure area under the curve (AUC) and (C) Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Calculated from baseline blood insulin and glucose levels, indicates an index of insulin resistance. Males at the medium exposure level show a significant increase in HOMA-IR as over control. Single stars indicate p-values<0.05, when compared to controls. Bars represent standard error.

Mentions: Overall, baseline blood glucose did not differ between exposure groups in females (Fig. 5a). At a single time point (t = 15 min), 16 ppm exposed females had significantly increased blood glucose compared to controls (p = 0.01), but not at any other time point (Fig. S2a). Females also had no significant differences in insulin overall or at any time point (Fig. 5b). Overall, among males, there were no significant differences in blood glucose at baseline (Fig. 5a). At a single time point (t = 120 min), 2.1 ppm exposed male mice had a significantly increased blood glucose (p = 0.05) (Fig. S2a). However overall male insulin levels did differ, with 16 ppm exposed males having significantly increased insulin levels (p = 0.01), compared to controls (Fig. 5b). Furthermore, at each time point they maintained increased insulin levels compared to controls at t = 15 min (p = 0.01), t = 30 min (p = 0.03), t = 60 min (p = 0.05), and t = 120 min (p = 0.03), with a significantly increased area under the curve (AUC p = 0.02), indicating greater total insulin production throughout the test, compared to controls (Figs. 5b & S2b). The homeostasis model assessment-estimated insulin resistance (HOMA-IR) was significantly increased in 16 ppm exposed males (p = 0.01) compared to controls. There were no differences in HOMA-IR among females (Fig. 5c).


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)

Blood Insulin and Glucose (9 months).(A) Glucose (mg/dl) measured by a fasting oral glucose tolerance AUC did not differ in either males or females. (B) Insulin (ng/ml) is increased in males at the medium exposure area under the curve (AUC) and (C) Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Calculated from baseline blood insulin and glucose levels, indicates an index of insulin resistance. Males at the medium exposure level show a significant increase in HOMA-IR as over control. Single stars indicate p-values<0.05, when compared to controls. Bars represent standard error.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0104273-g005: Blood Insulin and Glucose (9 months).(A) Glucose (mg/dl) measured by a fasting oral glucose tolerance AUC did not differ in either males or females. (B) Insulin (ng/ml) is increased in males at the medium exposure area under the curve (AUC) and (C) Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Calculated from baseline blood insulin and glucose levels, indicates an index of insulin resistance. Males at the medium exposure level show a significant increase in HOMA-IR as over control. Single stars indicate p-values<0.05, when compared to controls. Bars represent standard error.
Mentions: Overall, baseline blood glucose did not differ between exposure groups in females (Fig. 5a). At a single time point (t = 15 min), 16 ppm exposed females had significantly increased blood glucose compared to controls (p = 0.01), but not at any other time point (Fig. S2a). Females also had no significant differences in insulin overall or at any time point (Fig. 5b). Overall, among males, there were no significant differences in blood glucose at baseline (Fig. 5a). At a single time point (t = 120 min), 2.1 ppm exposed male mice had a significantly increased blood glucose (p = 0.05) (Fig. S2a). However overall male insulin levels did differ, with 16 ppm exposed males having significantly increased insulin levels (p = 0.01), compared to controls (Fig. 5b). Furthermore, at each time point they maintained increased insulin levels compared to controls at t = 15 min (p = 0.01), t = 30 min (p = 0.03), t = 60 min (p = 0.05), and t = 120 min (p = 0.03), with a significantly increased area under the curve (AUC p = 0.02), indicating greater total insulin production throughout the test, compared to controls (Figs. 5b & S2b). The homeostasis model assessment-estimated insulin resistance (HOMA-IR) was significantly increased in 16 ppm exposed males (p = 0.01) compared to controls. There were no differences in HOMA-IR among females (Fig. 5c).

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