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.
Highlights
The developmental origins of health and disease (DOHaD) hypothesis posits that early life conditions and exposures, during sensitive windows of development, can have long-term health effects [1,2]
Bone measures of chronic Pb exposure have been both positively and negatively correlated with body mass index (BMI) at different ages, but findings may be related to differences in cross-sectional and longitudinal study designs [10,11]
One recent study of Pb exposure in mice followed a longitudinal design, the characterization of metabolic effects was restricted to body weight at 1 year of life [9]
Summary
The developmental origins of health and disease (DOHaD) hypothesis posits that early life conditions and exposures, during sensitive windows of development, can have long-term health effects [1,2]. Few human or animal studies have attempted a lifecourse approach to investigate the effects of early-life Pb exposure on the metabolism and body habitus. In human cohort studies of prenatal Pb exposure, weight and body mass index (BMI) have followed subjects into early childhood [6,15]. One recent study of Pb exposure in mice followed a longitudinal design, the characterization of metabolic effects was restricted to body weight at 1 year of life [9]
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