ArticleeLife2023
Succinate mediates inflammation-induced adrenocortical dysfunction.
Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
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- Tricarboxylic Acid Cycle Intermediates and Individual Ageing.Biomolecules · 2024Review
- Cellular succinate metabolism and signaling in inflammation: implications for therapeutic intervention.Frontiers in immunology · 2024Review
- Inflammation-induced adrenal dysfunction.Nature reviews. Endocrinology · 2023Article
- Fatty acid desaturase 2 determines the lipidomic landscape and steroidogenic function of the adrenal gland.Science advances · 2023Article
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Authors and funding
20 authors at 4 institutions in 3 countries.
Funding
Abstract
The hypothalamus-pituitary-adrenal (HPA) axis is activated in response to inflammation leading to increased production of anti-inflammatory glucocorticoids by the adrenal cortex, thereby representing an endogenous feedback loop. However, severe inflammation reduces the responsiveness of the adrenal gland to adrenocorticotropic hormone (ACTH), although the underlying mechanisms are poorly understood. Here, we show by transcriptomic, proteomic, and metabolomic analyses that LPS-induced systemic inflammation triggers profound metabolic changes in steroidogenic adrenocortical cells, including downregulation of the TCA cycle and oxidative phosphorylation, in mice. Inflammation disrupts the TCA cycle at the level of succinate dehydrogenase (SDH), leading to succinate accumulation and disturbed steroidogenesis. Mechanistically, IL-1β reduces SDHB expression through upregulation of DNA methyltransferase 1 (DNMT1) and methylation of the
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.