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Publication
Developmental exposure to DDT or DDE alters sympathetic innervation of brown
adipose in adult female mice.
Authors vonderEmbse AN, Elmore SE, Jackson KB, Habecker BA, Manz KE, Pennell KD, Lein
PJ, La Merrill MA
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal Environmental health : a global access science source
Year 2021
Date Published 4/1/2021
Volume : Pages 20 : 37
PubMed Reference 33794904
Abstract Exposure to the bioaccumulative pesticide dichlorodiphenyltrichloroethane (DDT)
and its metabolite dichlorodiphenyldichloroethylene (DDE) has been associated
with increased risk of insulin resistance and obesity in humans and experimental
animals. These effects appear to be mediated by reduced brown adipose tissue
(BAT) thermogenesis, which is regulated by the sympathetic nervous system.
Although the neurotoxicity of DDT is well-established, whether DDT alters
sympathetic innervation of BAT is unknown. We hypothesized that perinatal
exposure to DDT or DDE promotes thermogenic dysfunction by interfering with
sympathetic regulation of BAT thermogenesis., Pregnant C57BL/6?J mice were
administered environmentally relevant concentrations of DDTs (p,p'-DDT and
o,p'-DDT) or DDE (p,p'-DDE), 1.7?mg/kg and 1.31?mg/kg, respectively, from
gestational day 11.5 to postnatal day 5 by oral gavage, and longitudinal body
temperature was recorded in male and female offspring. At 4?months of age,
metabolic parameters were measured in female offspring via indirect calorimetry
with or without the ß3 adrenergic receptor agonist, CL 316,243.
Immunohistochemical and neurochemical analyses of sympathetic neurons
innervating BAT were evaluated., We observed persistent thermogenic impairment
in adult female, but not male, mice perinatally exposed to DDTs or p,p'-DDE.
Perinatal DDTs exposure significantly impaired metabolism in adult female mice,
an effect rescued by treatment with CL 316,243 immediately prior to calorimetry
experiments. Neither DDTs nor p,p'-DDE significantly altered BAT morphology or
the concentrations of norepinephrine and its metabolite DHPG in the BAT of
DDTs-exposed mice. However, quantitative immunohistochemistry revealed a 20%
decrease in sympathetic axons innervating BAT in adult female mice perinatally
exposed to DDTs, but not p,p'-DDE, and 48 and 43% fewer synapses in stellate
ganglia of mice exposed to either DDTs or p,p'-DDE, respectively, compared to
control., These data demonstrate that perinatal exposure to DDTs or p,p'-DDE
impairs thermogenesis by interfering with patterns of connectivity in
sympathetic circuits that regulate BAT.




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