scholarly journals Developmental exposure to DDT or DDE alters sympathetic innervation of brown adipose in adult female mice

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Annalise N. vonderEmbse ◽  
Sarah E. Elmore ◽  
Kyle B. Jackson ◽  
Beth A. Habecker ◽  
Katherine E. Manz ◽  
...  
Keyword(s):  
Adult Female ◽  
Sympathetic Neurons ◽  
Sympathetic Innervation ◽  
Female Offspring ◽  
Perinatal Exposure ◽  
Female Mice ◽  
Cl 316,243 ◽  
Brown Adipose ◽  
Increased Risk ◽  
Sympathetic Regulation

Abstract Background 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. Methods 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 β3 adrenergic receptor agonist, CL 316,243. Immunohistochemical and neurochemical analyses of sympathetic neurons innervating BAT were evaluated. Results 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. Conclusions 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. Graphical abstract

scholarly journals Developmental Exposure to DDT or DDE Alters Sympathetic Innervation of Brown Adipose in Adult Female Mice

2020 ◽  
Author(s):  
Annalise N vonderEmbse ◽  
Sarah E Elmore ◽  
Kyle B Jackson ◽  
Beth A Habecker ◽  
Katherine E Manz ◽  
...  
Keyword(s):  
Adult Female ◽  
Sympathetic Neurons ◽  
Sympathetic Innervation ◽  
Female Offspring ◽  
Developmental Exposure ◽  
Female Mice ◽  
Cl 316,243 ◽  
Brown Adipose ◽  
Increased Risk ◽  
Sympathetic Regulation

Abstract Background: 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. Methods: Pregnant C57BL/6J mice were exposed by oral gavage to environmentally relevant concentrations of DDT (1.7 mg/kg) or DDE (1.31 mg/kg) from gestational day 11.5 to postnatal day 5, 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 β3 adrenergic receptor agonist, CL 316,243. Immunohistochemical and neurochemical analyses of sympathetic neurons innervating BAT were evaluated.Results: We observed persistent thermogenic impairment in adult female, but not male, mice perinatally exposed to DDT or DDE. Perinatal DDT exposure significantly impaired metabolism in adult female mice, an effect rescued by treatment with CL 316,243 immediately prior to calorimetry experiments. Neither DDT nor DDE significantly altered BAT morphology or the concentrations of norepinephrine and its metabolite DHPG in the BAT of DDT-exposed mice. However, quantitative immunohistochemistry revealed a 20% decrease in sympathetic axons innervating BAT in adult female mice perinatally exposed to DDT, but not DDE, and 48% and 43% fewer synapses in stellate ganglia of mice exposed to either DDT or DDE, respectively, compared to control. Conclusions: These data demonstrate that perinatal DDT and DDE exposure impairs thermogenesis by interfering with patterns of connectivity in sympathetic circuits that regulate BAT.

scholarly journals Neuronal Modulation of Brown Adipose Activity Through Perturbation of White Adipocyte Lipogenesis

2018 ◽  
Author(s):  
Adilson Guilherme ◽  
David J Pedersen ◽  
Felipe Henriques ◽  
Alexander H. Bedard ◽  
Elizabeth Henchey ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Fatty Acid Synthase ◽  
Sympathetic Neurons ◽  
Sympathetic Innervation ◽  
Long Distance ◽  
Brown Adipocytes ◽  
White Adipocyte ◽  
Brown Adipose ◽  
Beige Adipocytes

ABSTRACTWhite adipose tissue (WAT) secretes factors to communicate with other metabolic organs to maintain energy homeostasis. We previously reported that perturbation of adipocyte de novo lipogenesis (DNL) by deletion of fatty acid synthase (FASN) causes expansion of sympathetic neurons within white adipose tissue (WAT) and the appearance of “beige” adipocytes. Here we report evidence that white adipocyte DNL activity is also coupled to neuronal regulation and thermogenesis in brown adipose tissue (BAT). Induced deletion of FASN in all adipocytes in mature mice (iAdFASNKO) enhanced sympathetic innervation and neuronal activity as well as UCP1 expression in both WAT and BAT. In contrast, selective ablation of FASN in brown adipocytes of mice (iUCP1FASNKO) failed to modulate sympathetic innervation and the thermogenic program in BAT. Surprisingly, DNL in brown adipocytes was also dispensable in maintaining euthermia when UCP1FASNKO mice were cold-exposed. These results indicate that DNL in white adipocytes influences long distance signaling to BAT, which can modify BAT sympathetic innervation and expression of genes involved in thermogenesis.

Anxiety in adult female mice following perinatal exposure to chlorpyrifos

2010 ◽  
Vol 32 (2) ◽  
pp. 234-239 ◽  
Author(s):  
Jean-Baptiste Braquenier ◽  
Etienne Quertemont ◽  
Ezio Tirelli ◽  
Jean-Christophe Plumier
Keyword(s):  
Adult Female ◽  
Perinatal Exposure ◽  
Female Mice

scholarly journals Perinatal Exposure of Mice to the Pesticide DDT Impairs Energy Expenditure and Metabolism in Adult Female Offspring

PLoS ONE ◽  
2014 ◽  
Vol 9 (7) ◽  
pp. e103337 ◽  
Author(s):  
Michele La Merrill ◽  
Emma Karey ◽  
Erin Moshier ◽  
Claudia Lindtner ◽  
Michael R. La Frano ◽  
...  
Keyword(s):  
Energy Expenditure ◽  
Adult Female ◽  
Female Offspring ◽  
Perinatal Exposure

scholarly journals Perinatal maternal chronic exposure to dibutyl phthalate promotes visceral obesity in adult female offspring

2021 ◽  
Author(s):  
Kunyan Zhou ◽  
Ran Cheng ◽  
Meina Yang ◽  
Xiaoyang Shen ◽  
Xiaoyan Luo ◽  
...  
Keyword(s):  
Adult Female ◽  
Dibutyl Phthalate ◽  
Corn Oil ◽  
Visceral Obesity ◽  
Female Offspring ◽  
Perinatal Exposure ◽  
Fat Percentage ◽  
Protein Levels ◽  
Significant Difference ◽  
Visceral Adipose

IntroductionMaternal exposure to dibutyl phthalate (DBP) may result in glucolipid dysfunction in female offspring. However, the underlying mechanisms remain elusive. We hypothesized that chronic maternal DBP exposure could induce abnormal metabolism of glucolipid.Materials and methodsSprague-Dawley rats were intraperitoneally injected with different doses of DBP, estradiol, and corn oil from gestational day 7 until the end of lactation. The weights, visceral fat percentage, serum lipid, insulin and glucose, protein levels of PI3K signal pathway in muscle were detected in F1 female offspring.ResultsAlthough the birth weight of F1 female offspring was not different among groups, the weights were heavier in DBP groups from postnatal day 7 to adult (P<0.001). The visceral adipose percentage in adult female offspring was increased by perinatal exposure to DBP (P<0.001). Decreased serum levels of triglyceride (P<0.0001), fasting glucose (P=0.004), prolactin (P=0.006), HOMA-IR (P=0.014) were found in female offspring exposed to DBP, but no difference for fasting insulin, total cholesterol, adiponectin. Increased protein levels of p-AKT, but decreased PTEN and GPR30 were observed in muscle of female offspring in DBP group, but without significant difference. None difference was observed for the protein levels of PI3K, AKT, GLUT4, InsR and IRS-1.ConclusionMaternal perinatal exposure to DBP induced obesity and accumulation of visceral adipose tissue for the adult female offspring. Serum glucolipid and local signal transduction of PTEN/PI3K/AKT pathway in muscle were not adversely affected by perinatal exposure to DBP for adult female offspring.

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