Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact

Citations to this article

PAHSAs enhance hepatic and systemic insulin sensitivity through direct and indirect mechanisms
Peng Zhou, … , Dionicio Siegel, Barbara B. Kahn
Peng Zhou, … , Dionicio Siegel, Barbara B. Kahn
Published August 26, 2019
Citation Information: J Clin Invest. 2019;129(10):4138-4150. https://doi.org/10.1172/JCI127092.
View: Text | PDF
Research Article Endocrinology Metabolism Article has an altmetric score of 10

PAHSAs enhance hepatic and systemic insulin sensitivity through direct and indirect mechanisms

  • Text
  • PDF
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.

Authors

Peng Zhou, Anna Santoro, Odile D. Peroni, Andrew T. Nelson, Alan Saghatelian, Dionicio Siegel, Barbara B. Kahn

×

Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 Total
Citations: 4 9 5 10 11 9 2 50
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2020 (9)

Title and authors Publication Year
Adipocyte lipolysis: from molecular mechanisms of regulation to disease and therapeutics
A Yang, EP Mottillo
Biochemical Journal 2020
Long-term intake of 9-PAHPA or 9-OAHPA modulates favorably the basal metabolism and exerts an insulin sensitizing effect in obesogenic diet-fed mice
M Benlebna, L Balas, B Bonafos, L Pessemesse, G Fouret, C Vigor, S Gaillet, J Grober, F Bernex, JF Landrier, O Kuda, T Durand, C Coudray, F Casas, C Feillet-Coudray
European Journal of Nutrition 2020
Mechanisms of insulin resistance related to white, beige, and brown adipocytes
MP Czech
Molecular Metabolism 2020
AIG1 and ADTRP are endogenous hydrolases of fatty acid esters of hydroxy fatty acids (FAHFAs) in mice
ME Ertunc, BP Kok, WH Parsons, JG Wang, D Tan, CJ Donaldson, AF Pinto, JM Vaughan, N Ngo, KM Lum, CL Henry, AR Coppola, MJ Niphakis, BF Cravatt, E Saez, A Saghatelian
The Journal of biological chemistry 2020
ChREBP-Mediated Regulation of Lipid Metabolism: Involvement of the Gut Microbiota, Liver, and Adipose Tissue
K Iizuka, K Takao, D Yabe
Frontiers in Endocrinology 2020
9-PAHSA Prevents Mitochondrial Dysfunction and Increases the Viability of Steatotic Hepatocytes
AR Moreira, S Rüschenbaum, S Schefczyk, U Hendgen-Cotta, T Rassaf, R Broering, M Hardtke-Wolenski, LE Buitrago-Molina
International journal of molecular sciences 2020
Adipose Tissue Lipokines: Recent Progress and Future Directions
VL Li, JT Kim, JZ Long
Diabetes 2020
Charge-switch derivatization of fatty acid esters of hydroxy fatty acids via gas-phase ion/ion reactions
CE Randolph, DL Marshall, SJ Blanksby, SA McLuckey
Analytica Chimica Acta 2020
FAHFAs Regulate the Proliferation of C2C12 Myoblasts and Induce a Shift toward a More Oxidative Phenotype in Mouse Skeletal Muscle
M Benlebna, L Balas, L Pessemesse, B Bonafos, G Fouret, L Pavlin, B Goustard, S Gaillet, T Durand, C Coudray, C Feillet-Coudray, F Casas
International journal of molecular sciences 2020

Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Blogged by 1
Posted by 5 X users
45 readers on Mendeley
See more details