ArticleFree radical biology & medicine2021
Ketogenesis alleviates TNFα-induced apoptosis and inflammatory responses in intestinal cells.
Article in Free radical biology & medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 51 citations in OpenAlex.
- Targeting cell death in Crohn's disease: from mechanisms to medicines.Cell death discovery · 2026Review
- Therapeutic effect of daucosterol on DSS-induced colitis in mice.BMC microbiology · 2025Article
- Ketone ester supplementation protects from experimental colitis via improved goblet cell differentiation and function.European journal of nutrition · 2025Article
- Dietary Supplementation with Chenodeoxycholic Acid or Ursodeoxycholic Acid Modulates Growth, Thyroid Status, and Hepatopancreatic-Intestinal Health in Juvenile Little Yellow CroakerAntioxidants (Basel, Switzerland) · 2025Article
- The Interplay between the Gut and Ketogenic Diets in Health and Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Not Just an Alternative Energy Source: Diverse Biological Functions of Ketone Bodies and Relevance of HMGCS2 to Health and Disease.Biomolecules · 2025Review
- Comprehensive Overview of Ketone Bodies in Cancer Metabolism: Mechanisms and Application.Biomedicines · 2025Review
- Article
- The green tea component (-)-epigallocatechin-3-gallate protects against cytokine-induced epithelial barrier damage in intestinal epithelial cells.Frontiers in pharmacology · 2025Article
- HMGCS2 and AMACR as potential targets linking mitochondrial dysfunction and ulcerative colitis.Scientific reports · 2024Article
- [Asperosaponin VI alleviates TNBS-induced Crohn's disease-like colitis in mice by reducing intestinal epithelial cell apoptosis via inhibiting the PI3K/AKT/NF-κB signaling pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Article
- Evaluation of Cross-Talk and Alleviate Potential of Cytotoxic Factors Induced by Deoxynivalenol in IPEC-J2 Cells Interference with Curcumin.International journal of molecular sciences · 2024Article
- Colonic ketogenesis, a microbiota-regulated process, contributes to blood ketones and protects against colitis in mice.The Biochemical journal · 2024Article
- Ginseng-derived nanoparticles alleviate inflammatory bowel disease via the TLR4/MAPK and p62/Nrf2/Keap1 pathways.Journal of nanobiotechnology · 2024Article
- Ketogenic diet in treating sepsis-related acquired weakness: is it friend or foe?Frontiers in nutrition · 2024Review
- Exploring the impacts of ketogenic diet on reversible hepatic steatosis: initial analysis in male mice.Frontiers in nutrition · 2024Article
- Establishment of a lipopolysaccharide-induced inflammation model of human fetal colon cells.Molecular biology reports · 2023Article
- The Ketogenic Diet in Colorectal Cancer: A Means to an End.International journal of molecular sciences · 2023Review
- Integrated Bioinformatics Analysis and Experimental Verification of Immune Cell Infiltration and the Related Core Genes in Ulcerative Colitis.Pharmacogenomics and personalized medicine · 2023Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The disturbance of strictly regulated self-regeneration in mammalian intestinal epithelium is associated with various intestinal disorders, particularly inflammatory bowel diseases (IBDs). TNFα, which plays a critical role in the pathogenesis of IBDs, has been reported to inhibit production of ketone bodies such as β-hydroxybutyrate (βHB). However, the role of ketogenesis in the TNFα-mediated pathological process is not entirely known. Here, we showed the regulation and role of HMGCS2, the rate-limiting enzyme of ketogenesis, in TNFα-induced apoptotic and inflammatory responses in intestinal epithelial cells. Treatment with TNFα dose-dependently decreased protein and mRNA expression of HMGCS2 and its product, βHB production in human colon cancer cell lines HT29 and Caco2 cells and mouse small intestinal organoids. Moreover, the repressed level of HMGCS2 protein was found in intestinal epithelium of IBD patients with Crohn's disease and ulcerative colitis as compared with normal tissues. Furthermore, knockdown of HMGCS2 enhanced and in contrast, HMGCS2 overexpression attenuated, the TNFα-induced apoptosis and expression of pro-inflammatory chemokines (CXCL1-3) in HT29, Caco2 cells and DLD1 cells, respectively. Treatment with βHB or rosiglitazone, an agonist of PPARγ, which increases ketogenesis, attenuated TNFα-induced apoptosis in the intestinal epithelial cells. Finally, HMGCS2 knockdown enhanced TNFα-induced reactive oxygen species (ROS) generation. In addition, hydrogen peroxide, the major ROS contributing to intestine injury, decreased HMGCS2 expression and βHB production in the intestinal cells and mouse organoids. Our findings demonstrate that increased ketogenesis attenuates TNFα-induced apoptosis and inflammation in intestinal cells, suggesting a protective role for ketogenesis in TNFα-induced intestinal pathologies.
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Registered trials
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