Objective: Maternal obesity (MO) increases the risk of later-life liver disease in offspring, especially in males. This may be due to impaired cytochrome P450 (CYP) enzyme activity driven by an altered maternal-fetal hormonal milieu. MO increases fetal cortisol concentrations that may increase CYP activity; however, glucocorticoid receptor (GR)-mediated signaling can be modulated by alternative GR isoform expression. We hypothesized that MO induces sex-specific changes in GR isoform expression and localization that contribute to reduced hepatic CYP activity.
Methods: Nonpregnant, nulliparous female baboons were assigned to either an ad libitum control diet or a high-fat, high-energy diet (HF-HED) at 9 months pre pregnancy. At 165 days' gestation (term = 180 days), fetal liver samples were collected (n = 6/sex/group). CYP activity was quantified using functional assays, and GR was measured using quantitative RT-PCR and Western blot.
Results: CYP3A activity was reduced in the HF-HED group, whereas CYP2B6 activity was reduced in HF-HED males only. Total GR expression was increased in the HF-HED group. Relative nuclear expression of the antagonistic GR isoform GRβ was increased in HF-HED males only.
Conclusions: Reduced CYP activity in HF-HED males may be driven in part by dampened hepatic-specific glucocorticoid signaling via altered GR isoform expression. These findings highlight targetable mechanisms that may reduce later-life sex-specific disease risk.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11421985 | PMC |
http://dx.doi.org/10.1002/oby.24124 | DOI Listing |
Sci Rep
January 2025
School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, China.
Yeast sex-hormone whole-cell biosensors are analytical tools characterized by long-time storage and low production cost. We engineered compact β-estradiol biosensors in S. cerevisiae cells by leveraging short (20-nt long) operators bound by the fusion protein LexA-ER-VP64-where ER is the human estrogen receptor and VP64 a strong viral activation domain.
View Article and Find Full Text PDFForensic Sci Int Genet
December 2024
Service de Pharmacologie-Toxicologie et Pharmacovigilance, Centre Hospitalo-Universitaire d'Angers, Angers, France.
Interpreting postmortem concentrations of 3,4-Methylenedioxymethamphetamine (MDMA) remains challenging due to the wide range of reported results and the potential idiosyncratic nature of MDMA toxicity. Consequently, forensic pathologists often rely on a body of evidence to establish conclusions regarding the cause and the manner of death in death involving MDMA. Given these issues, implementing pharmacogenetics' (PGx)' testing may be beneficial.
View Article and Find Full Text PDFInt Immunopharmacol
December 2024
Undergraduate Program, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia. Electronic address:
Immunomodulators play a crucial role in maintaining overall health and enhancing the body's defense against various diseases. In Indonesian traditional medicinal practices, meniran (Phyllanthus niruri L.) and temu mangga rhizome (Curcuma mangga Val) are well-regarded for their health benefits and therapeutic properties.
View Article and Find Full Text PDFPLoS One
December 2024
Division of Pharmacology, National Institute of Health Sciences, Kawasaki, Kanagawa, Japan.
Cardiotoxicity associated with hepatic metabolism and drug-drug interactions is a serious concern. Predicting drug toxicity using animals remains challenging due to species and ethical concerns, necessitating the need to develop alternative approaches. Drug cardiotoxicity associated with hepatic metabolism cannot be detected using a cardiomyocyte-only evaluation system.
View Article and Find Full Text PDFChembiochem
December 2024
The University of Adelaide, Department of Chemistry, North Terrace, 5005, Adelaide, AUSTRALIA.
The heme enzymes of the cytochrome P450 superfamily (CYPs) catalyse the selective hydroxylation of unactivated C-H bonds in organic molecules. There is great interest in applying these enzymes as biocatalysts with a focus on self-sufficient CYP 'fusion' enzymes, comprising a single polypeptide chain with the electron transfer components joined to the heme domain. Here we elucidate the function of the self-sufficient CYP116B46 fusion enzyme, from the thermophilic bacterium Tepidiphilus thermophilus.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!