Integrated omics analysis reveals sirtuin signaling is central to hepatic response to a high fructose diet

Abstract Background Dietary high fructose (HFr) is a known metabolic disruptor contributing to development of obesity and diabetes in Western societies. Initial molecular changes from exposure to HFr on liver metabolism may be essential to understand the perturbations leading to insulin resistance a...

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Autores principales:	Laura A. Cox, Jeannie Chan, Prahlad Rao, Zeeshan Hamid, Jeremy P. Glenn, Avinash Jadhav, Vivek Das, Genesio M. Karere, Ellen Quillen, Kylie Kavanagh, Michael Olivier
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	High fructose diet Integrated omics Transcriptomics Proteomics Metabolomics miRNA Biotechnology TP248.13-248.65 Genetics QH426-470
Acceso en línea:	https://doaj.org/article/027e176990914d9fa4b758efaea0c266
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spelling	oai:doaj.org-article:027e176990914d9fa4b758efaea0c2662021-12-05T12:17:14ZIntegrated omics analysis reveals sirtuin signaling is central to hepatic response to a high fructose diet10.1186/s12864-021-08166-01471-2164https://doaj.org/article/027e176990914d9fa4b758efaea0c2662021-12-01T00:00:00Zhttps://doi.org/10.1186/s12864-021-08166-0https://doaj.org/toc/1471-2164Abstract Background Dietary high fructose (HFr) is a known metabolic disruptor contributing to development of obesity and diabetes in Western societies. Initial molecular changes from exposure to HFr on liver metabolism may be essential to understand the perturbations leading to insulin resistance and abnormalities in lipid and carbohydrate metabolism. We studied vervet monkeys (Clorocebus aethiops sabaeus) fed a HFr (n=5) or chow diet (n=5) for 6 weeks, and obtained clinical measures of liver function, blood insulin, cholesterol and triglycerides. In addition, we performed untargeted global transcriptomics, proteomics, and metabolomics analyses on liver biopsies to determine the molecular impact of a HFr diet on coordinated pathways and networks that differed by diet. Results We show that integration of omics data sets improved statistical significance for some pathways and networks, and decreased significance for others, suggesting that multiple omics datasets enhance confidence in relevant pathway and network identification. Specifically, we found that sirtuin signaling and a peroxisome proliferator activated receptor alpha (PPARA) regulatory network were significantly altered in hepatic response to HFr. Integration of metabolomics and miRNAs data further strengthened our findings. Conclusions Our integrated analysis of three types of omics data with pathway and regulatory network analysis demonstrates the usefulness of this approach for discovery of molecular networks central to a biological response. In addition, metabolites aspartic acid and docosahexaenoic acid (DHA), protein ATG3, and genes ATG7, and HMGCS2 link sirtuin signaling and the PPARA network suggesting molecular mechanisms for altered hepatic gluconeogenesis from consumption of a HFr diet.Laura A. CoxJeannie ChanPrahlad RaoZeeshan HamidJeremy P. GlennAvinash JadhavVivek DasGenesio M. KarereEllen QuillenKylie KavanaghMichael OlivierBMCarticleHigh fructose dietIntegrated omicsTranscriptomicsProteomicsMetabolomicsmiRNABiotechnologyTP248.13-248.65GeneticsQH426-470ENBMC Genomics, Vol 22, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	High fructose diet Integrated omics Transcriptomics Proteomics Metabolomics miRNA Biotechnology TP248.13-248.65 Genetics QH426-470
spellingShingle	High fructose diet Integrated omics Transcriptomics Proteomics Metabolomics miRNA Biotechnology TP248.13-248.65 Genetics QH426-470 Laura A. Cox Jeannie Chan Prahlad Rao Zeeshan Hamid Jeremy P. Glenn Avinash Jadhav Vivek Das Genesio M. Karere Ellen Quillen Kylie Kavanagh Michael Olivier Integrated omics analysis reveals sirtuin signaling is central to hepatic response to a high fructose diet
description	Abstract Background Dietary high fructose (HFr) is a known metabolic disruptor contributing to development of obesity and diabetes in Western societies. Initial molecular changes from exposure to HFr on liver metabolism may be essential to understand the perturbations leading to insulin resistance and abnormalities in lipid and carbohydrate metabolism. We studied vervet monkeys (Clorocebus aethiops sabaeus) fed a HFr (n=5) or chow diet (n=5) for 6 weeks, and obtained clinical measures of liver function, blood insulin, cholesterol and triglycerides. In addition, we performed untargeted global transcriptomics, proteomics, and metabolomics analyses on liver biopsies to determine the molecular impact of a HFr diet on coordinated pathways and networks that differed by diet. Results We show that integration of omics data sets improved statistical significance for some pathways and networks, and decreased significance for others, suggesting that multiple omics datasets enhance confidence in relevant pathway and network identification. Specifically, we found that sirtuin signaling and a peroxisome proliferator activated receptor alpha (PPARA) regulatory network were significantly altered in hepatic response to HFr. Integration of metabolomics and miRNAs data further strengthened our findings. Conclusions Our integrated analysis of three types of omics data with pathway and regulatory network analysis demonstrates the usefulness of this approach for discovery of molecular networks central to a biological response. In addition, metabolites aspartic acid and docosahexaenoic acid (DHA), protein ATG3, and genes ATG7, and HMGCS2 link sirtuin signaling and the PPARA network suggesting molecular mechanisms for altered hepatic gluconeogenesis from consumption of a HFr diet.
format	article
author	Laura A. Cox Jeannie Chan Prahlad Rao Zeeshan Hamid Jeremy P. Glenn Avinash Jadhav Vivek Das Genesio M. Karere Ellen Quillen Kylie Kavanagh Michael Olivier
author_facet	Laura A. Cox Jeannie Chan Prahlad Rao Zeeshan Hamid Jeremy P. Glenn Avinash Jadhav Vivek Das Genesio M. Karere Ellen Quillen Kylie Kavanagh Michael Olivier
author_sort	Laura A. Cox
title	Integrated omics analysis reveals sirtuin signaling is central to hepatic response to a high fructose diet
title_short	Integrated omics analysis reveals sirtuin signaling is central to hepatic response to a high fructose diet
title_full	Integrated omics analysis reveals sirtuin signaling is central to hepatic response to a high fructose diet
title_fullStr	Integrated omics analysis reveals sirtuin signaling is central to hepatic response to a high fructose diet
title_full_unstemmed	Integrated omics analysis reveals sirtuin signaling is central to hepatic response to a high fructose diet
title_sort	integrated omics analysis reveals sirtuin signaling is central to hepatic response to a high fructose diet
publisher	BMC
publishDate	2021
url	https://doaj.org/article/027e176990914d9fa4b758efaea0c266
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Integrated omics analysis reveals sirtuin signaling is central to hepatic response to a high fructose diet

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