期刊
MOLECULAR NUTRITION & FOOD RESEARCH
卷 63, 期 23, 页码 -出版社
WILEY
DOI: 10.1002/mnfr.201900773
关键词
metabolomics; resilient regulation; RNA-Seq; short-term fructose overfeeding; SREBP-1
资金
- National Natural Science Foundation of China [81530102]
- Science and Technology Planning Project of Guangdong Province, China [2015A050502050, 2016B050501003]
- BBSRC [BB/K021281/1] Funding Source: UKRI
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. Therefore, an integrated omics analysis is carried out to investigate the consequences of short-term fructose overfeeding (SFO) and identify the underlying molecular mechanisms. Methods and results SFO of rats demonstrates obvious histopathological hepatic lipid accumulation and significant elevation in adiposity, total cholesterol, and fasting plasma glucose levels. Integrated omics analysis demonstrates that SFO disturbed metabolic homeostasis and initiated metabolic stress. Hepatic lipogenesis pathways are also negatively impacted by SFO. Analysis of molecular networks generated by ingenuity pathway analysis (IPA) implicates involvement of the extracellular signal regulated kinase (ERK) signaling pathway in SFO and its consequences. Moreover, it is identified that an inherent negative feedback regulation of hepatic sterol regulatory element binding protein 1 (SREBP1) plays an active role in regulating hepatic de novo lipogenesis. Conclusion The findings indicate that SFO disturbs metabolic homeostasis and that endogenous small molecules positively mediate SFO-induced metabolic adaption. The results also underline that an inherent regulatory mechanism of resilience occurs in response to fructose overconsumption, suggesting that efforts to maintain resilience can be a promising target to prevent and treat metabolic disorder-like conditions.
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