A novel, multitargeted endogenous metabolic modulator composition impacts metabolism, inflammation, and fibrosis in nonalcoholic steatohepatitis-relevant primary human cell models

Abstract Nonalcoholic steatohepatitis (NASH) is a complex metabolic disease of heterogeneous and multifactorial pathogenesis that may benefit from coordinated multitargeted interventions. Endogenous metabolic modulators (EMMs) encompass a broad set of molecular families, including amino acids and re...

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Autores principales:	Nadine Daou, Andreu Viader, Murat Cokol, Arianna Nitzel, Manu V. Chakravarthy, Raffi Afeyan, Tony Tramontin, Svetlana Marukian, Michael J. Hamill
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c2f374aab92a482f9c189e152af4110d
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spelling	oai:doaj.org-article:c2f374aab92a482f9c189e152af4110d2021-12-02T17:51:21ZA novel, multitargeted endogenous metabolic modulator composition impacts metabolism, inflammation, and fibrosis in nonalcoholic steatohepatitis-relevant primary human cell models10.1038/s41598-021-88913-12045-2322https://doaj.org/article/c2f374aab92a482f9c189e152af4110d2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88913-1https://doaj.org/toc/2045-2322Abstract Nonalcoholic steatohepatitis (NASH) is a complex metabolic disease of heterogeneous and multifactorial pathogenesis that may benefit from coordinated multitargeted interventions. Endogenous metabolic modulators (EMMs) encompass a broad set of molecular families, including amino acids and related metabolites and precursors. EMMs often serve as master regulators and signaling agents for metabolic pathways throughout the body and hold the potential to impact a complex metabolic disease like NASH by targeting a multitude of pathologically relevant biologies. Here, we describe a study of a novel EMM composition comprising five amino acids and an amino acid derivative (Leucine, Isoleucine, Valine, Arginine, Glutamine, and N-acetylcysteine [LIVRQNac]) and its systematic evaluation across multiple NASH-relevant primary human cell model systems, including hepatocytes, macrophages, and stellate cells. In these model systems, LIVRQNac consistently and simultaneously impacted biology associated with all three core pathophysiological features of NASH—metabolic, inflammatory, and fibrotic. Importantly, it was observed that while the individual constituent amino acids in LIVRQNac can impact specific NASH-related phenotypes in select cell systems, the complete combination was necessary to impact the range of disease-associated drivers examined. These findings highlight the potential of specific and potent multitargeted amino acid combinations for the treatment of NASH.Nadine DaouAndreu ViaderMurat CokolArianna NitzelManu V. ChakravarthyRaffi AfeyanTony TramontinSvetlana MarukianMichael J. HamillNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nadine Daou Andreu Viader Murat Cokol Arianna Nitzel Manu V. Chakravarthy Raffi Afeyan Tony Tramontin Svetlana Marukian Michael J. Hamill A novel, multitargeted endogenous metabolic modulator composition impacts metabolism, inflammation, and fibrosis in nonalcoholic steatohepatitis-relevant primary human cell models
description	Abstract Nonalcoholic steatohepatitis (NASH) is a complex metabolic disease of heterogeneous and multifactorial pathogenesis that may benefit from coordinated multitargeted interventions. Endogenous metabolic modulators (EMMs) encompass a broad set of molecular families, including amino acids and related metabolites and precursors. EMMs often serve as master regulators and signaling agents for metabolic pathways throughout the body and hold the potential to impact a complex metabolic disease like NASH by targeting a multitude of pathologically relevant biologies. Here, we describe a study of a novel EMM composition comprising five amino acids and an amino acid derivative (Leucine, Isoleucine, Valine, Arginine, Glutamine, and N-acetylcysteine [LIVRQNac]) and its systematic evaluation across multiple NASH-relevant primary human cell model systems, including hepatocytes, macrophages, and stellate cells. In these model systems, LIVRQNac consistently and simultaneously impacted biology associated with all three core pathophysiological features of NASH—metabolic, inflammatory, and fibrotic. Importantly, it was observed that while the individual constituent amino acids in LIVRQNac can impact specific NASH-related phenotypes in select cell systems, the complete combination was necessary to impact the range of disease-associated drivers examined. These findings highlight the potential of specific and potent multitargeted amino acid combinations for the treatment of NASH.
format	article
author	Nadine Daou Andreu Viader Murat Cokol Arianna Nitzel Manu V. Chakravarthy Raffi Afeyan Tony Tramontin Svetlana Marukian Michael J. Hamill
author_facet	Nadine Daou Andreu Viader Murat Cokol Arianna Nitzel Manu V. Chakravarthy Raffi Afeyan Tony Tramontin Svetlana Marukian Michael J. Hamill
author_sort	Nadine Daou
title	A novel, multitargeted endogenous metabolic modulator composition impacts metabolism, inflammation, and fibrosis in nonalcoholic steatohepatitis-relevant primary human cell models
title_short	A novel, multitargeted endogenous metabolic modulator composition impacts metabolism, inflammation, and fibrosis in nonalcoholic steatohepatitis-relevant primary human cell models
title_full	A novel, multitargeted endogenous metabolic modulator composition impacts metabolism, inflammation, and fibrosis in nonalcoholic steatohepatitis-relevant primary human cell models
title_fullStr	A novel, multitargeted endogenous metabolic modulator composition impacts metabolism, inflammation, and fibrosis in nonalcoholic steatohepatitis-relevant primary human cell models
title_full_unstemmed	A novel, multitargeted endogenous metabolic modulator composition impacts metabolism, inflammation, and fibrosis in nonalcoholic steatohepatitis-relevant primary human cell models
title_sort	novel, multitargeted endogenous metabolic modulator composition impacts metabolism, inflammation, and fibrosis in nonalcoholic steatohepatitis-relevant primary human cell models
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c2f374aab92a482f9c189e152af4110d
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A novel, multitargeted endogenous metabolic modulator composition impacts metabolism, inflammation, and fibrosis in nonalcoholic steatohepatitis-relevant primary human cell models

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