Combined metabolic activators therapy ameliorates liver fat in nonalcoholic fatty liver disease patients

Abstract Nonalcoholic fatty liver disease (NAFLD) refers to excess fat accumulation in the liver. In animal experiments and human kinetic study, we found that administration of combined metabolic activators (CMAs) promotes the oxidation of fat, attenuates the resulting oxidative stress, activates mi...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Mujdat Zeybel, Ozlem Altay, Muhammad Arif, Xiangyu Li, Hong Yang, Claudia Fredolini, Murat Akyildiz, Burcin Saglam, Mehmet Gokhan Gonenli, Dilek Ural, Woonghee Kim, Jochen M Schwenk, Cheng Zhang, Saeed Shoaie, Jens Nielsen, Mathias Uhlén, Jan Borén, Adil Mardinoglu
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	CMA multi‐omics NAFLD systems biology Biology (General) QH301-705.5 Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/458a964c837f412a952dd9635ecd9b5f
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:458a964c837f412a952dd9635ecd9b5f
record_format	dspace
spelling	oai:doaj.org-article:458a964c837f412a952dd9635ecd9b5f2021-11-11T11:30:48ZCombined metabolic activators therapy ameliorates liver fat in nonalcoholic fatty liver disease patients1744-429210.15252/msb.202110459https://doaj.org/article/458a964c837f412a952dd9635ecd9b5f2021-10-01T00:00:00Zhttps://doi.org/10.15252/msb.202110459https://doaj.org/toc/1744-4292Abstract Nonalcoholic fatty liver disease (NAFLD) refers to excess fat accumulation in the liver. In animal experiments and human kinetic study, we found that administration of combined metabolic activators (CMAs) promotes the oxidation of fat, attenuates the resulting oxidative stress, activates mitochondria, and eventually removes excess fat from the liver. Here, we tested the safety and efficacy of CMA in NAFLD patients in a placebo‐controlled 10‐week study. We found that CMA significantly decreased hepatic steatosis and levels of aspartate aminotransferase, alanine aminotransferase, uric acid, and creatinine, whereas found no differences on these variables in the placebo group after adjustment for weight loss. By integrating clinical data with plasma metabolomics and inflammatory proteomics as well as oral and gut metagenomic data, we revealed the underlying molecular mechanisms associated with the reduced hepatic fat and inflammation in NAFLD patients and identified the key players involved in the host–microbiome interactions. In conclusion, we showed that CMA can be used to develop a pharmacological treatment strategy in NAFLD patients.Mujdat ZeybelOzlem AltayMuhammad ArifXiangyu LiHong YangClaudia FredoliniMurat AkyildizBurcin SaglamMehmet Gokhan GonenliDilek UralWoonghee KimJochen M SchwenkCheng ZhangSaeed ShoaieJens NielsenMathias UhlénJan BorénAdil MardinogluWileyarticleCMAmulti‐omicsNAFLDsystems biologyBiology (General)QH301-705.5Medicine (General)R5-920ENMolecular Systems Biology, Vol 17, Iss 10, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	CMA multi‐omics NAFLD systems biology Biology (General) QH301-705.5 Medicine (General) R5-920
spellingShingle	CMA multi‐omics NAFLD systems biology Biology (General) QH301-705.5 Medicine (General) R5-920 Mujdat Zeybel Ozlem Altay Muhammad Arif Xiangyu Li Hong Yang Claudia Fredolini Murat Akyildiz Burcin Saglam Mehmet Gokhan Gonenli Dilek Ural Woonghee Kim Jochen M Schwenk Cheng Zhang Saeed Shoaie Jens Nielsen Mathias Uhlén Jan Borén Adil Mardinoglu Combined metabolic activators therapy ameliorates liver fat in nonalcoholic fatty liver disease patients
description	Abstract Nonalcoholic fatty liver disease (NAFLD) refers to excess fat accumulation in the liver. In animal experiments and human kinetic study, we found that administration of combined metabolic activators (CMAs) promotes the oxidation of fat, attenuates the resulting oxidative stress, activates mitochondria, and eventually removes excess fat from the liver. Here, we tested the safety and efficacy of CMA in NAFLD patients in a placebo‐controlled 10‐week study. We found that CMA significantly decreased hepatic steatosis and levels of aspartate aminotransferase, alanine aminotransferase, uric acid, and creatinine, whereas found no differences on these variables in the placebo group after adjustment for weight loss. By integrating clinical data with plasma metabolomics and inflammatory proteomics as well as oral and gut metagenomic data, we revealed the underlying molecular mechanisms associated with the reduced hepatic fat and inflammation in NAFLD patients and identified the key players involved in the host–microbiome interactions. In conclusion, we showed that CMA can be used to develop a pharmacological treatment strategy in NAFLD patients.
format	article
author	Mujdat Zeybel Ozlem Altay Muhammad Arif Xiangyu Li Hong Yang Claudia Fredolini Murat Akyildiz Burcin Saglam Mehmet Gokhan Gonenli Dilek Ural Woonghee Kim Jochen M Schwenk Cheng Zhang Saeed Shoaie Jens Nielsen Mathias Uhlén Jan Borén Adil Mardinoglu
author_facet	Mujdat Zeybel Ozlem Altay Muhammad Arif Xiangyu Li Hong Yang Claudia Fredolini Murat Akyildiz Burcin Saglam Mehmet Gokhan Gonenli Dilek Ural Woonghee Kim Jochen M Schwenk Cheng Zhang Saeed Shoaie Jens Nielsen Mathias Uhlén Jan Borén Adil Mardinoglu
author_sort	Mujdat Zeybel
title	Combined metabolic activators therapy ameliorates liver fat in nonalcoholic fatty liver disease patients
title_short	Combined metabolic activators therapy ameliorates liver fat in nonalcoholic fatty liver disease patients
title_full	Combined metabolic activators therapy ameliorates liver fat in nonalcoholic fatty liver disease patients
title_fullStr	Combined metabolic activators therapy ameliorates liver fat in nonalcoholic fatty liver disease patients
title_full_unstemmed	Combined metabolic activators therapy ameliorates liver fat in nonalcoholic fatty liver disease patients
title_sort	combined metabolic activators therapy ameliorates liver fat in nonalcoholic fatty liver disease patients
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/458a964c837f412a952dd9635ecd9b5f
work_keys_str_mv	AT mujdatzeybel combinedmetabolicactivatorstherapyamelioratesliverfatinnonalcoholicfattyliverdiseasepatients AT ozlemaltay combinedmetabolicactivatorstherapyamelioratesliverfatinnonalcoholicfattyliverdiseasepatients AT muhammadarif combinedmetabolicactivatorstherapyamelioratesliverfatinnonalcoholicfattyliverdiseasepatients AT xiangyuli combinedmetabolicactivatorstherapyamelioratesliverfatinnonalcoholicfattyliverdiseasepatients AT hongyang combinedmetabolicactivatorstherapyamelioratesliverfatinnonalcoholicfattyliverdiseasepatients AT claudiafredolini combinedmetabolicactivatorstherapyamelioratesliverfatinnonalcoholicfattyliverdiseasepatients AT muratakyildiz combinedmetabolicactivatorstherapyamelioratesliverfatinnonalcoholicfattyliverdiseasepatients AT burcinsaglam combinedmetabolicactivatorstherapyamelioratesliverfatinnonalcoholicfattyliverdiseasepatients AT mehmetgokhangonenli combinedmetabolicactivatorstherapyamelioratesliverfatinnonalcoholicfattyliverdiseasepatients AT dilekural combinedmetabolicactivatorstherapyamelioratesliverfatinnonalcoholicfattyliverdiseasepatients AT woongheekim combinedmetabolicactivatorstherapyamelioratesliverfatinnonalcoholicfattyliverdiseasepatients AT jochenmschwenk combinedmetabolicactivatorstherapyamelioratesliverfatinnonalcoholicfattyliverdiseasepatients AT chengzhang combinedmetabolicactivatorstherapyamelioratesliverfatinnonalcoholicfattyliverdiseasepatients AT saeedshoaie combinedmetabolicactivatorstherapyamelioratesliverfatinnonalcoholicfattyliverdiseasepatients AT jensnielsen combinedmetabolicactivatorstherapyamelioratesliverfatinnonalcoholicfattyliverdiseasepatients AT mathiasuhlen combinedmetabolicactivatorstherapyamelioratesliverfatinnonalcoholicfattyliverdiseasepatients AT janboren combinedmetabolicactivatorstherapyamelioratesliverfatinnonalcoholicfattyliverdiseasepatients AT adilmardinoglu combinedmetabolicactivatorstherapyamelioratesliverfatinnonalcoholicfattyliverdiseasepatients
_version_	1718439119230599168

Combined metabolic activators therapy ameliorates liver fat in nonalcoholic fatty liver disease patients

Ejemplares similares