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

BMC Genomics

Zeeshan Hamid¹  Genesio M. Karere²  Michael Olivier²  Avinash Jadhav²  Jeannie Chan²  Ellen Quillen²  Laura A. Cox³  Kylie Kavanagh⁴  Jeremy P. Glenn⁵  Vivek Das⁶  Prahlad Rao⁷ 

[1] Center for Precision Medicine, Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Medical Center Boulevard, NRC, G-floor, 27157, Winston-Salem, NC, USA;Center for Precision Medicine, Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Medical Center Boulevard, NRC, G-floor, 27157, Winston-Salem, NC, USA;Department of Genetics, Texas Biomedical Research Institute, 78245, San Antonio, TX, USA;Center for Precision Medicine, Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Medical Center Boulevard, NRC, G-floor, 27157, Winston-Salem, NC, USA;Department of Genetics, Texas Biomedical Research Institute, 78245, San Antonio, TX, USA;Southwest National Primate Research Center, Texas Biomedical Research Institute, 78245, San Antonio, TX, USA;Department of Pathology, Section on Comparative Medicine, Wake Forest School of Medicine, 27157, Winston-Salem, NC, USA;Center for Precision Medicine, Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Medical Center Boulevard, NRC, G-floor, 27157, Winston-Salem, NC, USA;Department of Pathology, Section on Comparative Medicine, Wake Forest School of Medicine, 27157, Winston-Salem, NC, USA;Department of Genetics, Texas Biomedical Research Institute, 78245, San Antonio, TX, USA;Southwest National Primate Research Center, Texas Biomedical Research Institute, 78245, San Antonio, TX, USA;Novo Nordisk Research Center, Seattle, WA, USA;University of Tennessee Health Science Center, Memphis, TN, USA;

关键词: High fructose diet;    Integrated omics;    Transcriptomics;    Proteomics;    Metabolomics;    miRNA;    Liver metabolism;    Diet;    Vervet;    Pathway analysis;   

DOI  :  10.1186/s12864-021-08166-0

来源: Springer

【 摘 要 】

BackgroundDietary 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.ResultsWe 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.ConclusionsOur 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.

【 授权许可】

CC BY