Omics Insights into Metabolic Stress and Resilience of Rats in Response to Short-term Fructose Overfeeding.



Li, Kun-Ping, Yuan, Min, He, Zhuo-Ru, Wu, Qi, Zhang, Chu-Mei, Lei, Zhi-Li, Rong, Xiang-Lu, Huang, Zebo, Turnbull, Jeremy E ORCID: 0000-0002-1791-754X and Guo, Jiao
(2019) Omics Insights into Metabolic Stress and Resilience of Rats in Response to Short-term Fructose Overfeeding. Molecular nutrition & food research. e1900773 - e1900773.

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Abstract

SCOPE:Considerable evidence supports the view that high-fructose intake is associated with increased and early incidence of obesity and dyslipidemia. However, knowledge on physiopathological alterations introduced by fructose overconsumption is lacking. We have therefore carried out an integrated omics analysis to investigate the consequences of short-term fructose overfeeding(SFO) and identify the underlying molecular mechanisms. METHODS AND RESULTS:SFO of rats demonstrated obvious histopathological hepatic lipid accumulation and significant elevation in adiposity, total cholesterol and fasting plasma glucose levels. Integrated omics analysis demonstrated that SFO disturbed metabolic homeostasis and initiated metabolic stress. Hepatic lipogenesis pathways were also negatively impacted by SFO. Analysis of molecular networks generated by IPA implicated involvement of the ERK signaling pathway in SFO and its consequences. Moreover, we identified that an inherent negative feedback regulation of hepatic SREBP1 plays an active role in regulating hepatic de novo lipogenesis. CONCLUSION:Our findings indicate that SFO disturbs metabolic homeostasis and that endogenous small molecules positively mediate SFO induced metabolic adaption. Our results also underline that an inherent regulatory mechanism of resilience occurs in response to fructose overconsumption, suggesting that efforts to maintain resilience could be a promising target to prevent and treat metabolic disorder-like conditions. This article is protected by copyright. All rights reserved.

Item Type: Article
Depositing User: Symplectic Admin
Date Deposited: 17 Sep 2019 08:01
Last Modified: 05 Nov 2020 04:11
DOI: 10.1002/mnfr.201900773
URI: http://livrepository.liverpool.ac.uk/id/eprint/3054820