Genomically anchored vitamin D receptor mediates an abundance of bioprotective actions elicited by its 1,25-dihydroxyvitamin D hormonal ligand

Haussler, Mark R.; Haussler, Carol A.; Jurutka, Peter W.

doi:10.1016/bs.vh.2022.12.008

Cited by 2 publications

(1 citation statement)

References 233 publications

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“…Other RXR relevant chemicals are BPA, TBT, phytanic acid, calcitriol, targretin, AGN194204, fludioxonil and 2,4-DTBP. Studies have indicated that they can interact with RXR and affect its activity, potentially disrupting signalling pathways mediated by RXR-containing heterodimers ( 84 , 87 , 88 , 160 , 170 , 194 , 195 , 202 , 226 , 253 , 254 ).…”

Section: Resultsmentioning

confidence: 99%

Addressing chemically-induced obesogenic metabolic disruption: selection of chemicals for in vitro human PPARα, PPARγ transactivation, and adipogenesis test methods

Ozcagli,

Kubickova,

Jacobs

2024

Front. Endocrinol.

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Whilst western diet and sedentary lifestyles heavily contribute to the global obesity epidemic, it is likely that chemical exposure may also contribute. A substantial body of literature implicates a variety of suspected environmental chemicals in metabolic disruption and obesogenic mechanisms. Chemically induced obesogenic metabolic disruption is not yet considered in regulatory testing paradigms or regulations, but this is an internationally recognised human health regulatory development need. An early step in the development of relevant regulatory test methods is to derive appropriate minimum chemical selection lists for the target endpoint and its key mechanisms, such that the test method can be suitably optimised and validated. Independently collated and reviewed reference and proficiency chemicals relevant for the regulatory chemical universe that they are intended to serve, assist regulatory test method development and validation, particularly in relation to the OECD Test Guidelines Programme. To address obesogenic mechanisms and modes of action for chemical hazard assessment, key initiating mechanisms include molecular-level Peroxisome Proliferator-Activated Receptor (PPAR) α and γ agonism and the tissue/organ-level key event of perturbation of the adipogenesis process that may lead to excess white adipose tissue. Here we present a critical literature review, analysis and evaluation of chemicals suitable for the development, optimisation and validation of human PPARα and PPARγ agonism and human white adipose tissue adipogenesis test methods. The chemical lists have been derived with consideration of essential criteria needed for understanding the strengths and limitations of the test methods. With a weight of evidence approach, this has been combined with practical and applied aspects required for the integration and combination of relevant candidate test methods into test batteries, as part of an Integrated Approach to Testing and Assessment for metabolic disruption. The proposed proficiency and reference chemical list includes a long list of negatives and positives (20 chemicals for PPARα, 21 for PPARγ, and 11 for adipogenesis) from which a (pre-)validation proficiency chemicals list has been derived.

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Section: Resultsmentioning

confidence: 99%

Addressing chemically-induced obesogenic metabolic disruption: selection of chemicals for in vitro human PPARα, PPARγ transactivation, and adipogenesis test methods

Ozcagli,

Kubickova,

Jacobs

2024

Front. Endocrinol.

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From the Sun to the Cell: Examining Obesity through the Lens of Vitamin D and Inflammation

Popa,

Niță,

Caba

et al. 2023

Metabolites

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Obesity affects more than one billion people worldwide and often leads to cardiometabolic chronic comorbidities. It induces senescence-related alterations in adipose tissue, and senescence is closely linked to obesity. Fully elucidating the pathways through which vitamin D exerts anti-inflammatory effects may improve our understanding of local adipose tissue inflammation and the pathogenesis of metabolic disorders. In this narrative review, we compiled and analyzed the literature from diverse academic sources, focusing on recent developments to provide a comprehensive overview of the effect of vitamin D on inflammation associated with obesity and senescence. The article reveals that the activation of the NF-κB (nuclear factor kappa B subunit 1) and NLRP3 inflammasome (nucleotide-binding domain, leucine-rich-containing, pyrin domain-containing-3) pathways through the toll-like receptors, which increases oxidative stress and cytokine release, is a common mechanism underlying inflammation associated with obesity and senescence, and it discusses the potential beneficial effect of vitamin D in alleviating the development of subclinical inflammation. Investigating the main target cells and pathways of vitamin D action in adipose tissue could help uncover complex mechanisms of obesity and cellular senescence. This review summarizes significant findings related to opportunities for improving metabolic health.

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Genomically anchored vitamin D receptor mediates an abundance of bioprotective actions elicited by its 1,25-dihydroxyvitamin D hormonal ligand

Cited by 2 publications

References 233 publications

Addressing chemically-induced obesogenic metabolic disruption: selection of chemicals for in vitro human PPARα, PPARγ transactivation, and adipogenesis test methods

Addressing chemically-induced obesogenic metabolic disruption: selection of chemicals for in vitro human PPARα, PPARγ transactivation, and adipogenesis test methods

From the Sun to the Cell: Examining Obesity through the Lens of Vitamin D and Inflammation

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