Cargando…

Identification of Accessible Hepatic Gene Signatures for Interindividual Variations in Nutrigenomic Response to Dietary Supplementation of Omega-3 Fatty Acids

Dietary supplementation is a widely adapted strategy to maintain nutritional balance for improving health and preventing chronic diseases. Conflicting results in studies of similar design, however, suggest that there is substantial heterogenicity in individuals’ responses to nutrients, and personali...

Descripción completa

Detalles Bibliográficos
Autores principales: Shi, Yu, Li, Ping, Jiang, Cheng-fei, Chen, Yi, Ma, Yonghe, Gupta, Nikhil, Ruan, Xiangbo, Cao, Haiming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926558/
https://www.ncbi.nlm.nih.gov/pubmed/33671567
http://dx.doi.org/10.3390/cells10020467
_version_ 1783659494172000256
author Shi, Yu
Li, Ping
Jiang, Cheng-fei
Chen, Yi
Ma, Yonghe
Gupta, Nikhil
Ruan, Xiangbo
Cao, Haiming
author_facet Shi, Yu
Li, Ping
Jiang, Cheng-fei
Chen, Yi
Ma, Yonghe
Gupta, Nikhil
Ruan, Xiangbo
Cao, Haiming
author_sort Shi, Yu
collection PubMed
description Dietary supplementation is a widely adapted strategy to maintain nutritional balance for improving health and preventing chronic diseases. Conflicting results in studies of similar design, however, suggest that there is substantial heterogenicity in individuals’ responses to nutrients, and personalized nutrition is required to achieve the maximum benefit of dietary supplementation. In recent years, nutrigenomics studies have been increasingly utilized to characterize the detailed genomic response to a specific nutrient, but it remains a daunting task to define the signatures responsible for interindividual variations to dietary supplements for tissues with limited accessibility. In this work, we used the hepatic response to omega-3 fatty acids as an example to probe such signatures. Through comprehensive analysis of nutrigenomic response to eicosapentaneoid acid (EPA) and/or docosahexaenoic acid (DHA) including both protein coding and long noncoding RNA (lncRNA) genes in human hepatocytes, we defined the EPA- and/or DHA-specific signature genes in hepatocytes. By analyzing gene expression variations in livers of healthy and relevant disease populations, we identified a set of protein coding and lncRNA signature genes whose responses to omega-3 fatty acid exhibit very high interindividual variabilities. The large variabilities of individual responses to omega-3 fatty acids were further validated in human hepatocytes from ten different donors. Finally, we profiled RNAs in exosomes isolated from the circulation of a liver-specific humanized mouse model, in which the humanized liver is the sole source of human RNAs, and confirmed the in vivo detectability of some signature genes, supporting their potential as biomarkers for nutrient response. Taken together, we have developed an efficient and practical procedure to identify nutrient-responsive gene signatures as well as accessible biomarkers for interindividual variations.
format Online
Article
Text
id pubmed-7926558
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-79265582021-03-04 Identification of Accessible Hepatic Gene Signatures for Interindividual Variations in Nutrigenomic Response to Dietary Supplementation of Omega-3 Fatty Acids Shi, Yu Li, Ping Jiang, Cheng-fei Chen, Yi Ma, Yonghe Gupta, Nikhil Ruan, Xiangbo Cao, Haiming Cells Article Dietary supplementation is a widely adapted strategy to maintain nutritional balance for improving health and preventing chronic diseases. Conflicting results in studies of similar design, however, suggest that there is substantial heterogenicity in individuals’ responses to nutrients, and personalized nutrition is required to achieve the maximum benefit of dietary supplementation. In recent years, nutrigenomics studies have been increasingly utilized to characterize the detailed genomic response to a specific nutrient, but it remains a daunting task to define the signatures responsible for interindividual variations to dietary supplements for tissues with limited accessibility. In this work, we used the hepatic response to omega-3 fatty acids as an example to probe such signatures. Through comprehensive analysis of nutrigenomic response to eicosapentaneoid acid (EPA) and/or docosahexaenoic acid (DHA) including both protein coding and long noncoding RNA (lncRNA) genes in human hepatocytes, we defined the EPA- and/or DHA-specific signature genes in hepatocytes. By analyzing gene expression variations in livers of healthy and relevant disease populations, we identified a set of protein coding and lncRNA signature genes whose responses to omega-3 fatty acid exhibit very high interindividual variabilities. The large variabilities of individual responses to omega-3 fatty acids were further validated in human hepatocytes from ten different donors. Finally, we profiled RNAs in exosomes isolated from the circulation of a liver-specific humanized mouse model, in which the humanized liver is the sole source of human RNAs, and confirmed the in vivo detectability of some signature genes, supporting their potential as biomarkers for nutrient response. Taken together, we have developed an efficient and practical procedure to identify nutrient-responsive gene signatures as well as accessible biomarkers for interindividual variations. MDPI 2021-02-22 /pmc/articles/PMC7926558/ /pubmed/33671567 http://dx.doi.org/10.3390/cells10020467 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Shi, Yu
Li, Ping
Jiang, Cheng-fei
Chen, Yi
Ma, Yonghe
Gupta, Nikhil
Ruan, Xiangbo
Cao, Haiming
Identification of Accessible Hepatic Gene Signatures for Interindividual Variations in Nutrigenomic Response to Dietary Supplementation of Omega-3 Fatty Acids
title Identification of Accessible Hepatic Gene Signatures for Interindividual Variations in Nutrigenomic Response to Dietary Supplementation of Omega-3 Fatty Acids
title_full Identification of Accessible Hepatic Gene Signatures for Interindividual Variations in Nutrigenomic Response to Dietary Supplementation of Omega-3 Fatty Acids
title_fullStr Identification of Accessible Hepatic Gene Signatures for Interindividual Variations in Nutrigenomic Response to Dietary Supplementation of Omega-3 Fatty Acids
title_full_unstemmed Identification of Accessible Hepatic Gene Signatures for Interindividual Variations in Nutrigenomic Response to Dietary Supplementation of Omega-3 Fatty Acids
title_short Identification of Accessible Hepatic Gene Signatures for Interindividual Variations in Nutrigenomic Response to Dietary Supplementation of Omega-3 Fatty Acids
title_sort identification of accessible hepatic gene signatures for interindividual variations in nutrigenomic response to dietary supplementation of omega-3 fatty acids
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926558/
https://www.ncbi.nlm.nih.gov/pubmed/33671567
http://dx.doi.org/10.3390/cells10020467
work_keys_str_mv AT shiyu identificationofaccessiblehepaticgenesignaturesforinterindividualvariationsinnutrigenomicresponsetodietarysupplementationofomega3fattyacids
AT liping identificationofaccessiblehepaticgenesignaturesforinterindividualvariationsinnutrigenomicresponsetodietarysupplementationofomega3fattyacids
AT jiangchengfei identificationofaccessiblehepaticgenesignaturesforinterindividualvariationsinnutrigenomicresponsetodietarysupplementationofomega3fattyacids
AT chenyi identificationofaccessiblehepaticgenesignaturesforinterindividualvariationsinnutrigenomicresponsetodietarysupplementationofomega3fattyacids
AT mayonghe identificationofaccessiblehepaticgenesignaturesforinterindividualvariationsinnutrigenomicresponsetodietarysupplementationofomega3fattyacids
AT guptanikhil identificationofaccessiblehepaticgenesignaturesforinterindividualvariationsinnutrigenomicresponsetodietarysupplementationofomega3fattyacids
AT ruanxiangbo identificationofaccessiblehepaticgenesignaturesforinterindividualvariationsinnutrigenomicresponsetodietarysupplementationofomega3fattyacids
AT caohaiming identificationofaccessiblehepaticgenesignaturesforinterindividualvariationsinnutrigenomicresponsetodietarysupplementationofomega3fattyacids