ArticleThe Journal of clinical investigation2019
PAHSAs enhance hepatic and systemic insulin sensitivity through direct and indirect mechanisms.
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 57 papers.
What it found
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The trial behind it
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Who cites it
57 citing papers in PubMed, 97 citations in OpenAlex.
- Acute aerobic exercise reveals that FAHFAs distinguish the metabolomes of overweight and normal-weight runners.JCI insight · 2022Trial
- Acute exercise-induced lipolysis and increase in levels of fatty acid esters of hydroxy fatty acids in adipose tissue are impaired in obese and aged mice.Experimental physiology · 2026Article
- Fatty acid esters of hydroxy fatty acids and alkyl-diacylglycerols: minor but bioactive components in human milk.Biochemical Society transactions · 2026Review
- FAHFAs are detected in postprandial chylomicron and VLDL fractions and can be released from TG estolides by LPL in vitro.Journal of lipid research · 2026Article
- Caspase-6 Controls Lipid and Energy Metabolism in Diet-Induced Obesity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- 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
- Immune system, inflammatory response, and regulated cell death in breast cancer research (Review).Oncology reports · 2026Review
- The effects of saturated fatty acid supplements on plasma and milk concentration of fatty acid esters of hydroxy fatty acids in dairy cows.JDS communications · 2025Article
- Transcriptome and Metabolome Profiles Reveal the Underlying Mechanism of Fat Deposition Changes in Three-Way Crossbred Yak for High-Quality Beef Production.Animals : an open access journal from MDPI · 2025Article
- Unraveling the complexities of diet induced obesity and glucolipid dysfunction in metabolic syndrome.Diabetology & metabolic syndrome · 2025Review
- Hyperinsulinemia-induced upregulation of adipocyte TPH2 contributes to peripheral serotonin production, metabolic dysfunction, and obesity.The Journal of clinical investigation · 2025Article
- 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
- Mechanisms of microplastics on gastrointestinal injury and liver metabolism disorder (Review).Molecular medicine reports · 2025Review
- Review
- Investigating the Pathogenesis and Treatment of Type 2 Diabetes from the Perspective of Adipose Tissue.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Review
- The role of adipose tissue dysfunction in hepatic insulin resistance and T2D.The Journal of endocrinology · 2024Review
- Review
- 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
- Inflammation causes insulin resistance in mice via interferon regulatory factor 3 (IRF3)-mediated reduction in FAHFA levels.Nature communications · 2024Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Palmitic acid esters of hydroxy stearic acids (PAHSAs) are bioactive lipids with antiinflammatory and antidiabetic effects. PAHSAs reduce ambient glycemia and improve glucose tolerance and insulin sensitivity in insulin-resistant aged chow- and high-fat diet-fed (HFD-fed) mice. Here, we aimed to determine the mechanisms by which PAHSAs improve insulin sensitivity. Both acute and chronic PAHSA treatment enhanced the action of insulin to suppress endogenous glucose production (EGP) in chow- and HFD-fed mice. Moreover, chronic PAHSA treatment augmented insulin-stimulated glucose uptake in glycolytic muscle and heart in HFD-fed mice. The mechanisms by which PAHSAs enhanced hepatic insulin sensitivity included direct and indirect actions involving intertissue communication between adipose tissue and liver. PAHSAs inhibited lipolysis directly in WAT explants and enhanced the action of insulin to suppress lipolysis during the clamp in vivo. Preventing the reduction of free fatty acids during the clamp with Intralipid infusion reduced PAHSAs' effects on EGP in HFD-fed mice but not in chow-fed mice. Direct hepatic actions of PAHSAs may also be important, as PAHSAs inhibited basal and glucagon-stimulated EGP directly in isolated hepatocytes through a cAMP-dependent pathway involving Gαi protein-coupled receptors. Thus, this study advances our understanding of PAHSA biology and the physiologic mechanisms by which PAHSAs exert beneficial metabolic effects.
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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.