PMID- 37820785
OWN - NLM
STAT- MEDLINE
DCOM- 20231106
LR  - 20240206
IS  - 1873-6351 (Electronic)
IS  - 0278-6915 (Print)
IS  - 0278-6915 (Linking)
VI  - 181
DP  - 2023 Nov
TI  - Hepatic cholesterol biosynthesis and dioxin-induced dysregulation: A multiscale 
      computational approach.
PG  - 114086
LID - S0278-6915(23)00488-X [pii]
LID - 10.1016/j.fct.2023.114086 [doi]
AB  - Humans are constantly exposed to lipophilic persistent organic pollutants (POPs) 
      that accumulate in fatty foods. Among the numerous POPs, dioxins, in particular 
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), can impact several organ systems. 
      While the hazard is clearly recognized, it is still difficult to develop a 
      comprehensive understanding of the overall health impacts of dioxins. As chemical 
      toxicity testing is steadily adopting new approach methodologies (NAMs), it 
      becomes imperative to develop computational models that can bridge the data gaps 
      between in vitro testing and in vivo outcomes. As an effort to address this 
      challenge, we propose a multiscale computational approach using a 
      "template-and-anchor" (T&A) structure. A template is a high-level umbrella model 
      that permits the integration of information from various, detailed anchor models. 
      In the present study, we use this T&A approach to describe the effect of TCDD on 
      cholesterol dynamics. Specifically, we represent hepatic cholesterol biosynthesis 
      as an anchor model that is perturbed by TCDD, leading to steatosis, along with 
      alterations of plasma cholesterol. In the future, incorporating pertinent 
      information from all anchor models into the template model will allow the 
      characterization of the global effects of dioxin, which can subsequently be 
      translated into overall - and ultimately personalized - human health risk 
      assessment.
CI  - Copyright (c) 2023 Elsevier Ltd. All rights reserved.
FAU - Kumbale, Carla M
AU  - Kumbale CM
AD  - Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, 
      GA 30332, USA. Electronic address: Ckumbale3@gatech.edu.
FAU - Zhang, Qiang
AU  - Zhang Q
AD  - Gangarosa Department of Environmental Health, Rollins School of Public Health, 
      Emory University, Atlanta, GA 30322, USA. Electronic address: 
      Qiang.zhang@emory.edu.
FAU - Voit, Eberhard O
AU  - Voit EO
AD  - Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, 
      GA 30332, USA. Electronic address: Eberhard.voit@bme.gatech.edu.
LA  - eng
GR  - P30 ES019776/ES/NIEHS NIH HHS/United States
GR  - P42 ES004911/ES/NIEHS NIH HHS/United States
PT  - Journal Article
DEP - 20231010
PL  - England
TA  - Food Chem Toxicol
JT  - Food and chemical toxicology : an international journal published for the British 
      Industrial Biological Research Association
JID - 8207483
RN  - 0 (Dioxins)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (Environmental Pollutants)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - Humans
MH  - *Dioxins/toxicity
MH  - *Polychlorinated Dibenzodioxins/toxicity/analysis
MH  - Liver
MH  - *Environmental Pollutants/toxicity
MH  - Cholesterol
PMC - PMC10841405
MID - NIHMS1940129
OTO - NOTNLM
OT  - Cholesterol
OT  - Dioxin
OT  - Mevalonate pathway
OT  - Steatosis
OT  - Systems biology
OT  - Template-and-anchor model
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/10/12 00:43
MHDA- 2023/11/06 06:43
PMCR- 2024/11/01
CRDT- 2023/10/11 19:36
PHST- 2023/05/25 00:00 [received]
PHST- 2023/09/18 00:00 [revised]
PHST- 2023/10/03 00:00 [accepted]
PHST- 2024/11/01 00:00 [pmc-release]
PHST- 2023/11/06 06:43 [medline]
PHST- 2023/10/12 00:43 [pubmed]
PHST- 2023/10/11 19:36 [entrez]
AID - S0278-6915(23)00488-X [pii]
AID - 10.1016/j.fct.2023.114086 [doi]
PST - ppublish
SO  - Food Chem Toxicol. 2023 Nov;181:114086. doi: 10.1016/j.fct.2023.114086. Epub 2023 
      Oct 10.