Abstract
Consistent with findings from experimental research in nonhuman primates exposed to early-life stress, children exposed to maltreatment are at high risk of detrimental physical health conditions, such as obesity and systemic inflammation. Because leptin is a key molecule involved in the regulation of both energy balance and immunity, we investigated abnormalities in leptin physiology among maltreated children. We measured leptin, body mass index and C-reactive protein in 170 12-year-old children members of the Environmental-Risk Longitudinal Twin Study, for whom we had prospectively-collected information on maltreatment exposure. We found that maltreated children exhibited blunted elevation in leptin levels in relation to increasing levels of physiological stimuli, adiposity and inflammation, compared with a group of non-maltreated children matched for gender, zygosity and socioeconomic status. These findings were also independent of key potential artifacts and confounders, such as time of day at sample collection, history of food insecurity, pubertal maturation and depressive symptoms. Furthermore, using birth weight as a proxy measure for leptin, we found that physiological abnormalities were presumably not present at birth in children who went on to be maltreated but only emerged over the course of childhood, after maltreatment exposure. Leptin deficiency may contribute to onset, persistence and progression of physical health problems in maltreated children.
Highlights
Because leptin is a key molecule involved in the regulation of both energy balance and immunity, we investigated possible differences in leptin physiology in maltreated vs non-maltreated children
We found no main effect of maltreatment on leptin levels (BMIadjusted: beta = − 0.08, P = 0.143), the association between Body mass index (BMI) and leptin was modified by maltreatment, with maltreated children showing blunted elevation in leptin levels in the manufacturer
We observed the expected significant positive association between inflammation and leptin. This association was modified by maltreatment status, with maltreated children showing blunted elevation in leptin levels in relation to increasing CRP levels compared with non-maltreated children
Summary
Maltreated children experience detrimental physical health consequences, such as obesity and systemic inflammation,[1,2] consistent with findings from experimental research in nonhuman primates exposed to early-life stress.[3,4] Because leptin is a key molecule involved in the regulation of both energy balance and immunity, we investigated possible differences in leptin physiology in maltreated vs non-maltreated children. Leptin is secreted by adipocytes in response to increasing levels of adiposity.[5] Leptin secretion stimulates hypothalamic neurons inducing downregulation of the neuropeptide Y and upregulation of the alpha-melanocyte-stimulating hormone, inhibits mesolimbic dopamine release and activates the sympathetic nervous system Through this neuroendocrine response, leptin secretion promotes decrease in energy intake and increase in energy expenditure, reducing its original secretory stimulus, adiposity. By potentiating the immune response and modulating cytokine secretion, leptin may promote effective resolution of the acute inflammatory response, reducing its original secretory stimulus This potential negative feedback mechanism appears to be disrupted in ob/ob mice,[6] who have deficient leptin response to increasing levels of inflammation and, show more severe outcomes after administration of pro-inflammatory stimuli (for example, lipopolysaccharide, interleukin-1b, tumor necrosis factor-alpha, ozone). In the present study we provide initial evidence that the effects of early-life stress on leptin reactivity described in experimental animal models translate to humans, and that effect modification by early-life stress applies to later heterologous physiological stimulation by adiposity and inflammation, consistent with abnormalities described in ob/ob mice
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