PMID- 36277707
OWN - NLM
STAT- MEDLINE
DCOM- 20221027
LR  - 20240422
IS  - 1664-2392 (Print)
IS  - 1664-2392 (Electronic)
IS  - 1664-2392 (Linking)
VI  - 13
DP  - 2022
TI  - Developmental exposure to indoor flame retardants and hypothalamic molecular 
      signatures: Sex-dependent reprogramming of lipid homeostasis.
PG  - 997304
LID - 10.3389/fendo.2022.997304 [doi]
LID - 997304
AB  - Polybrominated diphenyl ethers (PBDEs) are a class of flame-retardant 
      organohalogen pollutants that act as endocrine/neuroendocrine disrupting 
      chemicals (EDCs). In humans, exposure to brominated flame retardants (BFR) or 
      other environmentally persistent organic pollutants (POPs) such as 
      polychlorinated biphenyls (PCBs) and novel organophosphate flame retardants has 
      been associated with increasing trends of diabetes and metabolic disease. 
      However, the effects of PBDEs on metabolic processes and their associated 
      sex-dependent features are poorly understood. The metabolic-disrupting effects of 
      perinatal exposure to industrial penta-PBDE mixture, DE-71, on male and female 
      progeny of C57BL/6N mouse dams were examined in adulthood. Dams were exposed to 
      environmentally relevant doses of PBDEs daily for 10 weeks (p.o.): 0.1 (L-DE-71) 
      and 0.4 mg/kg/d (H-DE-71) and offspring parameters were compared to corn oil 
      vehicle controls (VEH/CON). The following lipid metabolism indices were measured: 
      plasma cholesterol, triglycerides, adiponectin, leptin, and liver lipids. L-DE-71 
      female offspring were particularly affected, showing hypercholesterolemia, 
      elevated liver lipids and fasting plasma leptin as compared to same-sex VEH/CON, 
      while L- and H-DE-71 male F1 only showed reduced plasma adiponectin. Using the 
      quantitative Folch method, we found that mean liver lipid content was 
      significantly elevated in L-DE-71 female offspring compared to controls. Oil Red 
      O staining revealed fatty liver in female offspring and dams. General measures of 
      adiposity, body weight, white and brown adipose tissue (BAT), and lean and fat 
      mass were weighed or measured using EchoMRI. DE-71 did not produce abnormal 
      adiposity, but decreased BAT depots in L-DE-71 females and males relative to 
      same-sex VEH/CON. To begin to address potential central mechanisms of deregulated 
      lipid metabolism, we used RT-qPCR to quantitate expression of hypothalamic genes 
      in energy-regulating circuits that control lipid homeostasis. Both doses of DE-71 
      sex-dependently downregulated hypothalamic expression of Lepr, Stat3, Mc4r, Agrp, 
      Gshr in female offspring while H-DE-71 downregulated Npy in exposed females 
      relative to VEH/CON. In contrast, exposed male offspring displayed upregulated 
      Stat3 and Mc4r. Intestinal barrier integrity was measured using FITC-dextran 
      since it can lead to systemic inflammation that leads to liver damage and 
      metabolic disease, but was not affected by DE-71 exposure. These findings 
      indicate that maternal transfer of PBDEs disproportionately endangers female 
      offspring to lipid metabolic reprogramming that may exaggerate risk for adult 
      metabolic disease.
CI  - Copyright (c) 2022 Kozlova, Denys, Benedum, Valdez, Enriquez, Bishay, Chinthirla, 
      Truong, Krum, DiPatrizio, Deol, Martins-Green and Curras-Collazo.
FAU - Kozlova, Elena V
AU  - Kozlova EV
AD  - Department of Molecular, Cell & Systems Biology, University of California, 
      Riverside, Riverside, CA, United States.
AD  - Neuroscience Graduate Program, University of California, Riverside, Riverside, 
      CA, United States.
FAU - Denys, Maximillian E
AU  - Denys ME
AD  - Department of Molecular, Cell & Systems Biology, University of California, 
      Riverside, Riverside, CA, United States.
FAU - Benedum, Jonathan
AU  - Benedum J
AD  - Department of Molecular, Cell & Systems Biology, University of California, 
      Riverside, Riverside, CA, United States.
FAU - Valdez, Matthew C
AU  - Valdez MC
AD  - Department of Molecular, Cell & Systems Biology, University of California, 
      Riverside, Riverside, CA, United States.
FAU - Enriquez, Dave
AU  - Enriquez D
AD  - Department of Molecular, Cell & Systems Biology, University of California, 
      Riverside, Riverside, CA, United States.
FAU - Bishay, Anthony E
AU  - Bishay AE
AD  - Department of Molecular, Cell & Systems Biology, University of California, 
      Riverside, Riverside, CA, United States.
FAU - Chinthirla, Bhuvaneswari D
AU  - Chinthirla BD
AD  - Department of Molecular, Cell & Systems Biology, University of California, 
      Riverside, Riverside, CA, United States.
FAU - Truong, Edward
AU  - Truong E
AD  - Department of Molecular, Cell & Systems Biology, University of California, 
      Riverside, Riverside, CA, United States.
FAU - Krum, Julia M
AU  - Krum JM
AD  - Department of Molecular, Cell & Systems Biology, University of California, 
      Riverside, Riverside, CA, United States.
FAU - DiPatrizio, Nicholas V
AU  - DiPatrizio NV
AD  - Biomedical Sciences, School of Medicine, University of California, Riverside, 
      Riverside, CA, United States.
FAU - Deol, Poonamjot
AU  - Deol P
AD  - Department of Molecular, Cell & Systems Biology, University of California, 
      Riverside, Riverside, CA, United States.
FAU - Martins-Green, Manuela
AU  - Martins-Green M
AD  - Department of Molecular, Cell & Systems Biology, University of California, 
      Riverside, Riverside, CA, United States.
FAU - Curras-Collazo, Margarita C
AU  - Curras-Collazo MC
AD  - Department of Molecular, Cell & Systems Biology, University of California, 
      Riverside, Riverside, CA, United States.
LA  - eng
GR  - L30 DK114978/DK/NIDDK NIH HHS/United States
GR  - R01 DK119498/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220930
PL  - Switzerland
TA  - Front Endocrinol (Lausanne)
JT  - Frontiers in endocrinology
JID - 101555782
RN  - 0 (Adiponectin)
RN  - 0 (Agouti-Related Protein)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - 8001-30-7 (Corn Oil)
RN  - 0 (Endocrine Disruptors)
RN  - 0 (Environmental Pollutants)
RN  - 0 (Flame Retardants)
RN  - 0 (Halogenated Diphenyl Ethers)
RN  - 0 (Leptin)
RN  - 0 (Organophosphates)
RN  - 7REL09ZX35 (pentabromodiphenyl ether)
RN  - 0 (Persistent Organic Pollutants)
RN  - DFC2HB4I0K (Polychlorinated Biphenyls)
RN  - 0 (Triglycerides)
SB  - IM
MH  - Animals
MH  - Female
MH  - Male
MH  - Mice
MH  - Pregnancy
MH  - Adiponectin
MH  - Agouti-Related Protein
MH  - Cholesterol
MH  - Corn Oil
MH  - *Endocrine Disruptors/toxicity
MH  - *Environmental Pollutants/toxicity
MH  - *Flame Retardants/toxicity
MH  - Halogenated Diphenyl Ethers/toxicity
MH  - Homeostasis
MH  - Leptin
MH  - Mice, Inbred C57BL
MH  - Organophosphates
MH  - Persistent Organic Pollutants
MH  - *Polychlorinated Biphenyls
MH  - Triglycerides
MH  - Sex Factors
PMC - PMC9580103
OTO - NOTNLM
OT  - dyslipidemia (DLP)
OT  - endocrine-disrupting chemical (EDC)
OT  - fatty liver
OT  - hypothalamus
OT  - leptin - adiponectin
OT  - maternal
OT  - metabolic syndrome & type II diabetes
OT  - polybrominated diphenyl ethers (PBDEs)
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/10/25 06:00
MHDA- 2022/10/26 06:00
PMCR- 2022/01/01
CRDT- 2022/10/24 04:37
PHST- 2022/07/18 00:00 [received]
PHST- 2022/08/25 00:00 [accepted]
PHST- 2022/10/24 04:37 [entrez]
PHST- 2022/10/25 06:00 [pubmed]
PHST- 2022/10/26 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fendo.2022.997304 [doi]
PST - epublish
SO  - Front Endocrinol (Lausanne). 2022 Sep 30;13:997304. doi: 
      10.3389/fendo.2022.997304. eCollection 2022.