scholarly journals Maternal Transfer of Environmentally Relevant Polybrominated Diphenyl Ethers (PBDEs) Produces a Diabetic Phenotype and Disrupts Glucoregulatory Hormones and Hepatic Endocannabinoids in Adult Mouse Female Offspring

2020 ◽  
Author(s):  
Elena V. Kozlova ◽  
Bhuvaneswari D. Chinthirla ◽  
Pedro A. Pérez ◽  
Nicholas V. DiPatrizio ◽  
Donovan A. Argueta ◽  
...  
Keyword(s):  
Polybrominated Diphenyl Ethers ◽  
Ex Vivo ◽  
Time Windows ◽  
Female Offspring ◽  
Exposure Model ◽  
Maternal Transfer ◽  
Tissue Mass ◽  
Brown Adipose ◽  
Diphenyl Ethers

AbstractPolybrominated diphenyl ethers (PBDEs) are brominated flame retardant chemicals and environmental contaminants with endocrine-disrupting properties that are associated with diabetes and metabolic syndrome in humans. However, their diabetogenic actions are not completely characterized or understood. In this study, we investigated the effects of DE-71, a commercial penta-mixture of PBDEs, on glucose regulatory parameters in a perinatal exposure model using female C57Bl/6 mice. Results from in vivo glucose and insulin tolerance tests and ex vivo analyses showed that DE-71 produced fasting hyperglycemia, glucose intolerance, reduced sensitivity and delayed glucose clearance after insulin challenge, and exaggerated hepatic endocannabinoid tone in F1 offspring exposed to 0.1 mg/kg DE-71 relative to control. DE-71 effects on F0 dams were more limited indicating that indirect exposure to developing offspring is more detrimental. Other ex vivo glycemic correlates occur more generally in exposed F0 and F1, i.e., reduced plasma insulin and altered glucoregulatory endocrines, exaggerated sympathoadrenal activity, decreased thermogenic brown adipose tissue mass and reduced hepatic glutamate dehydrogenase enzymatic activity. Hepatic PBDE congener analysis indicated maternal transfer of BDE-28 and −153 to F1 at a collective level of 200 ng/g lipid, in range with maximum values detected in serum of human females. Given the persistent diabetogenic phenotype, especially pronounced in female offspring after developmental exposure to environmentally relevant levels of DE-71, additional animal studies should be conducted that further characterize PBDE-induced diabetic pathophysiology and identify critical developmental time windows of susceptibility. Longitudinal human studies should also be conducted to determine the risk of long-lasting metabolic consequences after maternal transfer of PBDEs during early-life development.

scholarly journals Maternal transfer of environmentally relevant polybrominated diphenyl ethers (PBDEs) produces a diabetic phenotype and disrupts glucoregulatory hormones and hepatic endocannabinoids in adult mouse female offspring

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Elena V. Kozlova ◽  
Bhuvaneswari D. Chinthirla ◽  
Pedro A. Pérez ◽  
Nicholas V. DiPatrizio ◽  
Donovan A. Argueta ◽  
...  
Keyword(s):  
Polybrominated Diphenyl Ethers ◽  
Ex Vivo ◽  
Time Windows ◽  
Female Offspring ◽  
Exposure Model ◽  
Maternal Transfer ◽  
Tissue Mass ◽  
Brown Adipose ◽  
Diphenyl Ethers

Abstract Polybrominated diphenyl ethers (PBDEs) are brominated flame retardant chemicals and environmental contaminants with endocrine-disrupting properties that are associated with diabetes and metabolic syndrome in humans. However, their diabetogenic actions are not completely characterized or understood. In this study, we investigated the effects of DE-71, a commercial penta-mixture of PBDEs, on glucoregulatory parameters in a perinatal exposure model using female C57Bl/6 mice. Results from in vivo glucose and insulin tolerance tests and ex vivo analyses revealed fasting hyperglycemia, glucose intolerance, reduced sensitivity and delayed glucose clearance after insulin challenge, decreased thermogenic brown adipose tissue mass, and exaggerated hepatic endocannabinoid tone in F1 offspring exposed to 0.1 mg/kg DE-71 relative to control. DE-71 effects on F0 dams were more limited indicating that indirect exposure to developing offspring is more detrimental. Other ex vivo glycemic correlates occurred more generally in exposed F0 and F1, i.e., reduced plasma insulin and altered glucoregulatory endocrines, exaggerated sympathoadrenal activity and reduced hepatic glutamate dehydrogenase enzymatic activity. Hepatic PBDE congener analysis indicated maternal transfer of BDE-28 and -153 to F1 at a collective level of 200 ng/g lipid, in range with maximum values detected in serum of human females. Given the persistent diabetogenic phenotype, especially pronounced in female offspring after developmental exposure to environmentally relevant levels of DE-71, additional animal studies should be conducted that further characterize PBDE-induced diabetic pathophysiology and identify critical developmental time windows of susceptibility. Longitudinal human studies should also be conducted to determine the risk of long-lasting metabolic consequences after maternal transfer of PBDEs during early-life development.

scholarly journals JAZF1 heterozygous knockout mice show altered adipose development and metabolism

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jain Jeong ◽  
Soyoung Jang ◽  
Song Park ◽  
Wookbong Kwon ◽  
Si-Yong Kim ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Knockout Mice ◽  
Metabolic Disorders ◽  
Adipocyte Differentiation ◽  
Zinc Finger Protein ◽  
Tissue Mass ◽  
In Vivo Models ◽  
Brown Adipose

Abstract Background Juxtaposed with another zinc finger protein 1 (JAZF1) is associated with metabolic disorders, including type 2 diabetes mellitus (T2DM). Several studies showed that JAZF1 and body fat mass are closely related. We attempted to elucidate the JAZF1 functions on adipose development and related metabolism using in vitro and in vivo models. Results The JAZF1 expression was precisely regulated during adipocyte differentiation of 3T3-L1 preadipocyte and mouse embryonic fibroblasts (MEFs). Homozygous JAZF1 deletion (JAZF1-KO) resulted in impaired adipocyte differentiation in MEF. The JAZF1 role in adipocyte differentiation was demonstrated by the regulation of PPARγ—a key regulator of adipocyte differentiation. Heterozygous JAZF1 deletion (JAZF1-Het) mice fed a normal diet (ND) or a high-fat diet (HFD) had less adipose tissue mass and impaired glucose homeostasis than the control (JAZF1-Cont) mice. However, other metabolic organs, such as brown adipose tissue and liver, were negligible effect on JAZF1 deficiency. Conclusion Our findings emphasized the JAZF1 role in adipocyte differentiation and related metabolism through the heterozygous knockout mice. This study provides new insights into the JAZF1 function in adipose development and metabolism, informing strategies for treating obesity and related metabolic disorders.

scholarly journals Dopamine receptor D1- and D2-agonists do not spark brown adipose tissue thermogenesis in mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Francesca-Maria Raffaelli ◽  
Julia Resch ◽  
Rebecca Oelkrug ◽  
K. Alexander Iwen ◽  
Jens Mittag
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Dopamine Receptor ◽  
Ex Vivo ◽  
Potential Target ◽  
D2 Agonist ◽  
Obesity And Diabetes ◽  
Brown Adipose

AbstractBrown adipose tissue (BAT) thermogenesis is considered a potential target for treatment of obesity and diabetes. In vitro data suggest dopamine receptor signaling as a promising approach; however, the biological relevance of dopamine receptors in the direct activation of BAT thermogenesis in vivo remains unclear. We investigated BAT thermogenesis in vivo in mice using peripheral administration of D1-agonist SKF38393 or D2-agonist Sumanirole, infrared thermography, and in-depth molecular analyses of potential target tissues; and ex vivo in BAT explants to identify direct effects on key thermogenic markers. Acute in vivo treatment with the D1- or D2-agonist caused a short spike or brief decrease in BAT temperature, respectively. However, repeated daily administration did not induce lasting effects on BAT thermogenesis. Likewise, neither agonist directly affected Ucp1 or Dio2 mRNA expression in BAT explants. Taken together, the investigated agonists do not seem to exert lasting and physiologically relevant effects on BAT thermogenesis after peripheral administration, demonstrating that D1- and D2-receptors in iBAT are unlikely to constitute targets for obesity treatment via BAT activation.

scholarly journals Gene Deletion Mutants Reveal a Role for Semaphorin Receptors of the Plexin-B Family in Mechanisms Underlying Corticogenesis

2009 ◽  
Vol 30 (3) ◽  
pp. 764-780 ◽  
Author(s):  
A. Hirschberg ◽  
S. Deng ◽  
A. Korostylev ◽  
E. Paldy ◽  
M. R. Costa ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Ex Vivo ◽  
Time Windows ◽  
Expression Patterns ◽  
Cortical Development ◽  
Critical Time ◽  
Dependent Manner ◽  
Semaphorin 4D ◽  
Developing Neurons

ABSTRACT Semaphorins and their receptors, plexins, are emerging as key regulators of various aspects of neural and nonneural development. Semaphorin 4D (Sema4D) and B-type plexins demonstrate distinct expression patterns over critical time windows during the development of the murine neocortex. Here, analysis of mice genetically lacking plexin-B1 or plexin-B2 revealed the significance of Sema4D-plexin-B signaling in cortical development. Deficiency of plexin-B2 resulted in abnormal cortical layering and defective migration and differentiation of several subtypes of cortical neurons, including Cajal-Retzius cells, GABAergic interneurons, and principal cells in vivo. In contrast, a lack of plexin-B1 did not impact on cortical development in vivo. In various ex vivo assays on embryonic forebrain, Sema4D enhanced the radial and tangential migration of developing neurons in a plexin-B2-dependent manner. These results suggest that Sema4D-plexin-B2 interactions regulate mechanisms underlying cell specification, differentiation, and migration during corticogenesis.

scholarly journals Direct anabolic three carbon metabolism via propionate to a six carbon metabolite occurs in human heart and in vivo across mouse tissues

2019 ◽  
Author(s):  
Mary T. Doan ◽  
Michael D. Neinast ◽  
Erika L Varner ◽  
Kenneth Bedi ◽  
David Bartee ◽  
...  
Keyword(s):  
Human Heart ◽  
Ex Vivo ◽  
Tibialis Anterior Muscle ◽  
Whole Body ◽  
List Type ◽  
Isotope Tracing ◽  
Brown Adipose ◽  
Mouse Tissues

AbstractAnabolic metabolism of carbon in mammals is mediated via the one and two carbon carriers S-adenosyl methionine and acetyl-coenzyme A (acetyl-CoA). In contrast, anabolic metabolism using three carbon units via propionate is not thought to occur. Mammals are primarily thought to oxidize the 3-carbon short chain fatty acid propionate by shunting propionyl-CoA to succinyl-CoA for entry into the TCA cycle. We found that this may not be absolute and that in mammals one non-oxidative fate of two units of propionyl-CoA is to condense to a six-carbon trans-2-methyl-2-pentenoyl-CoA (2M2PE-CoA). We confirmed this pathway using purified protein extracts provided limited substrates and confirmed the product with a synthetic standard. In whole-body in vivo stable isotope tracing with infusion of 13C-labeled valine achieving steady state, 2M2PE-CoA formed via propionyl-CoA in multiple murine tissues including heart, kidney, and to a lesser degree in brown adipose tissue, liver, and tibialis anterior muscle. Using ex vivo isotope tracing, we found that 2M2PE-CoA formed in human myocardial tissue incubated with propionate to a limited extent. While the complete enzymology of this pathway remains to be elucidated, these results confirm the in vivo existence of at least one anabolic three to six carbon reaction conserved in humans and mice that utilizes three carbons via propionate.Highlights- Synthesis and confirmation of structure 2-methyl-2-pentenoyl-CoA- In vivo fate of valine across organs includes formation of a 6-carbon metabolite from propionyl-CoA- Ex vivo metabolism of propionate in the human heart includes direct anabolism to a 6-carbon product- In both cases, this reaction occurred at physiologically relevant concentrations of propionate and valine- In vitro this pathway requires propionyl-CoA and NADH/NADPH as substrates

scholarly journals Ex Vivo and In Vivo Evaluation of the Norepinephrine Transporter Ligand [11C]MRB for Brown Adipose Tissue Imaging

2012 ◽  
Vol 39 (7) ◽  
pp. 1081-1086 ◽  
Author(s):  
Shu-fei Lin ◽  
Xiaoning Fan ◽  
Catherine Weikart Yeckel ◽  
David Weinzimmer ◽  
Tim Mulnix ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Ex Vivo ◽  
Norepinephrine Transporter ◽  
Tissue Imaging ◽  
In Vivo Evaluation ◽  
Brown Adipose

Bioaccumulation, maternal transfer and elimination of polybrominated diphenyl ethers in wild frogs

Chemosphere ◽  
2011 ◽  
Vol 84 (7) ◽  
pp. 972-978 ◽  
Author(s):  
Peng-Yan Liu ◽  
Guo-Dong Du ◽  
Ya-Xian Zhao ◽  
Yun-Song Mu ◽  
Ai-Qian Zhang ◽  
...  
Keyword(s):  
Polybrominated Diphenyl Ethers ◽  
Maternal Transfer ◽  
Diphenyl Ethers
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