ArticleThe Journal of clinical investigation2019
PAHSAs attenuate immune responses and promote β cell survival in autoimmune diabetic mice.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 87 citations in OpenAlex.
- Fatty acid esters of hydroxy fatty acids and alkyl-diacylglycerols: minor but bioactive components in human milk.Biochemical Society transactions · 2026Review
- Beyond bystanders: How β cell stress shapes the autoimmune response in T1D.Science translational medicine · 2026Review
- ATGL-catalyzed biosynthesis mediates the upregulation of fatty acid hydroxy fatty acids (FAHFA) levels in white adipose tissue with fasting.The Journal of biological chemistry · 2026Article
- Senotherapeutics for metabolic disease and diabetic complications.Journal of internal medicine · 2026Review
- Comparative analysis of bioactivities of leaf extracts from wild plant speciesFrontiers in pharmacology · 2026Article
- The measurement, regulation and biological activity of FAHFAs.Nature chemical biology · 2025Review
- S-9-PAHSA Protects Against High-Fat Diet-Induced Diabetes-Associated Cognitive Impairment via Gut Microbiota Regulation.CNS neuroscience & therapeutics · 2025Article
- Investigating the Pathogenesis and Treatment of Type 2 Diabetes from the Perspective of Adipose Tissue.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Review
- Beneficial metabolic effects of PAHSAs depend on the gut microbiota in diet-induced obese mice but not in chow-fed mice.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Regulation of β-cell death by ADP-ribosylhydrolase ARH3 via lipid signaling in insulitis.Cell communication and signaling : CCS · 2024Article
- Lipotoxicity as a therapeutic target in obesity and diabetic cardiomyopathy.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2024Review
- β Cell Stress and Endocrine Function During T1D: What Is Next to Discover?Endocrinology · 2023Article
- A dataset of branched fatty acid esters of hydroxy fatty acids diversity in foods.Scientific data · 2023Article
- The Metabolomic Characteristics and Dysregulation of Fatty Acid Esters of Hydroxy Fatty Acids in Breast Cancer.Metabolites · 2023Article
- Mitogen-Activated Protein Kinase and Nuclear Hormone Receptor Crosstalk in Cancer Immunotherapy.International journal of molecular sciences · 2023Review
- Lipid remodeling of adipose tissue in metabolic health and disease.Experimental & molecular medicine · 2023Review
- Polyunsaturated Fatty Acids: Conversion to Lipid Mediators, Roles in Inflammatory Diseases and Dietary Sources.International journal of molecular sciences · 2023Review
- Physiological and pathological roles of lipogenesis.Nature metabolism · 2023Review
- PAHSAs reduce cellular senescence and protect pancreatic beta cells from metabolic stress through regulation of Mdm2/p53.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Palmitic acid esters of hydroxy stearic acids (PAHSAs) are endogenous antidiabetic and antiinflammatory lipids. Here, we show that PAHSAs protect against type 1 diabetes (T1D) and promote β cell survival and function. Daily oral PAHSA administration to nonobese diabetic (NOD) mice delayed the onset of T1D and markedly reduced the incidence of T1D, whether PAHSAs were started before or after insulitis was established. PAHSAs reduced T and B cell infiltration and CD4+ and CD8+ T cell activation, while increasing Treg activation in pancreata of NOD mice. PAHSAs promoted β cell proliferation in both NOD mice and MIN6 cells and increased the number of β cells in NOD mice. PAHSAs attenuated cytokine-induced apoptotic and necrotic β cell death and increased β cell viability. The mechanism appears to involve a reduction of ER stress and MAPK signaling, since PAHSAs lowered ER stress in NOD mice, suppressed thapsigargin-induced PARP cleavage in human islets, and attenuated ERK1/2 and JNK1/2 activation in MIN6 cells. This appeared to be mediated in part by glucagon-like peptide 1 receptor (GLP-1R) and not the G protein-coupled receptor GPR40. PAHSAs also prevented impairment of glucose-stimulated insulin secretion and improved glucose tolerance in NOD mice. Thus, PAHSAs delayed the onset of T1D and reduced its incidence by attenuating immune responses and exerting direct protective effects on β cell survival and function.
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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.