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Distinct biological activities of isomers from several families of branched fatty acid esters of hydroxy fatty acids (FAHFAs)

Branched fatty acid esters of hydroxy fatty acids (FAHFAs) are endogenous lipids with antidiabetic and anti-inflammatory effects. Each FAHFA family consists of esters with different acyl chains and multiple isomers with branch points at different carbons. Some FAHFAs, including palmitic acid hydroxy...

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Autores principales: Aryal, Pratik, Syed, Ismail, Lee, Jennifer, Patel, Rucha, Nelson, Andrew T., Siegel, Dionicio, Saghatelian, Alan, Kahn, Barbara B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479484/
https://www.ncbi.nlm.nih.gov/pubmed/34418413
http://dx.doi.org/10.1016/j.jlr.2021.100108
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author Aryal, Pratik
Syed, Ismail
Lee, Jennifer
Patel, Rucha
Nelson, Andrew T.
Siegel, Dionicio
Saghatelian, Alan
Kahn, Barbara B.
author_facet Aryal, Pratik
Syed, Ismail
Lee, Jennifer
Patel, Rucha
Nelson, Andrew T.
Siegel, Dionicio
Saghatelian, Alan
Kahn, Barbara B.
author_sort Aryal, Pratik
collection PubMed
description Branched fatty acid esters of hydroxy fatty acids (FAHFAs) are endogenous lipids with antidiabetic and anti-inflammatory effects. Each FAHFA family consists of esters with different acyl chains and multiple isomers with branch points at different carbons. Some FAHFAs, including palmitic acid hydroxy stearic acids (PAHSAs), improve insulin sensitivity and glucose tolerance in mice by enhancing glucose-stimulated insulin secretion (GSIS), insulin-stimulated glucose transport, and insulin action to suppress hepatic glucose production and reducing adipose tissue inflammation. However, little is known about the biological effects of other FAHFAs. Here, we investigated whether PAHSAs, oleic acid hydroxy stearic acid, palmitoleic acid hydroxy stearic acid, and stearic acid hydroxy stearic acid potentiate GSIS in β-cells and human islets, insulin-stimulated glucose uptake in adipocytes, and anti-inflammatory effects in immune cells. We also investigated whether they activate G protein–coupled receptor 40, which mediates the effects of PAHSAs on insulin secretion and sensitivity in vivo. We show that many FAHFAs potentiate GSIS, activate G protein–coupled receptor 40, and attenuate LPS-induced chemokine and cytokine expression and secretion and phagocytosis in immune cells. However, fewer FAHFAs augment insulin-stimulated glucose uptake in adipocytes. S-9-PAHSA, but not R-9-PAHSA, potentiated GSIS and glucose uptake, while both stereoisomers had anti-inflammatory effects. FAHFAs containing unsaturated acyl chains with higher branching from the carboxylate head group are more likely to potentiate GSIS, whereas FAHFAs with lower branching are more likely to be anti-inflammatory. This study provides insight into the specificity of the biological actions of different FAHFAs and could lead to the development of FAHFAs to treat metabolic and immune-mediated diseases.
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spelling pubmed-84794842021-10-04 Distinct biological activities of isomers from several families of branched fatty acid esters of hydroxy fatty acids (FAHFAs) Aryal, Pratik Syed, Ismail Lee, Jennifer Patel, Rucha Nelson, Andrew T. Siegel, Dionicio Saghatelian, Alan Kahn, Barbara B. J Lipid Res Research Article Branched fatty acid esters of hydroxy fatty acids (FAHFAs) are endogenous lipids with antidiabetic and anti-inflammatory effects. Each FAHFA family consists of esters with different acyl chains and multiple isomers with branch points at different carbons. Some FAHFAs, including palmitic acid hydroxy stearic acids (PAHSAs), improve insulin sensitivity and glucose tolerance in mice by enhancing glucose-stimulated insulin secretion (GSIS), insulin-stimulated glucose transport, and insulin action to suppress hepatic glucose production and reducing adipose tissue inflammation. However, little is known about the biological effects of other FAHFAs. Here, we investigated whether PAHSAs, oleic acid hydroxy stearic acid, palmitoleic acid hydroxy stearic acid, and stearic acid hydroxy stearic acid potentiate GSIS in β-cells and human islets, insulin-stimulated glucose uptake in adipocytes, and anti-inflammatory effects in immune cells. We also investigated whether they activate G protein–coupled receptor 40, which mediates the effects of PAHSAs on insulin secretion and sensitivity in vivo. We show that many FAHFAs potentiate GSIS, activate G protein–coupled receptor 40, and attenuate LPS-induced chemokine and cytokine expression and secretion and phagocytosis in immune cells. However, fewer FAHFAs augment insulin-stimulated glucose uptake in adipocytes. S-9-PAHSA, but not R-9-PAHSA, potentiated GSIS and glucose uptake, while both stereoisomers had anti-inflammatory effects. FAHFAs containing unsaturated acyl chains with higher branching from the carboxylate head group are more likely to potentiate GSIS, whereas FAHFAs with lower branching are more likely to be anti-inflammatory. This study provides insight into the specificity of the biological actions of different FAHFAs and could lead to the development of FAHFAs to treat metabolic and immune-mediated diseases. American Society for Biochemistry and Molecular Biology 2021-08-18 /pmc/articles/PMC8479484/ /pubmed/34418413 http://dx.doi.org/10.1016/j.jlr.2021.100108 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Article
Aryal, Pratik
Syed, Ismail
Lee, Jennifer
Patel, Rucha
Nelson, Andrew T.
Siegel, Dionicio
Saghatelian, Alan
Kahn, Barbara B.
Distinct biological activities of isomers from several families of branched fatty acid esters of hydroxy fatty acids (FAHFAs)
title Distinct biological activities of isomers from several families of branched fatty acid esters of hydroxy fatty acids (FAHFAs)
title_full Distinct biological activities of isomers from several families of branched fatty acid esters of hydroxy fatty acids (FAHFAs)
title_fullStr Distinct biological activities of isomers from several families of branched fatty acid esters of hydroxy fatty acids (FAHFAs)
title_full_unstemmed Distinct biological activities of isomers from several families of branched fatty acid esters of hydroxy fatty acids (FAHFAs)
title_short Distinct biological activities of isomers from several families of branched fatty acid esters of hydroxy fatty acids (FAHFAs)
title_sort distinct biological activities of isomers from several families of branched fatty acid esters of hydroxy fatty acids (fahfas)
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479484/
https://www.ncbi.nlm.nih.gov/pubmed/34418413
http://dx.doi.org/10.1016/j.jlr.2021.100108
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