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

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. 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.

A High‐Fat High‐Fructose Diet Dysregulates the Homeostatic Crosstalk Between Gut Microbiome, Metabolome, and Immunity in an Experimental Model of Obesity

“…Some commercial software can generate meaningful algorithmically networks to understand biological significance of complex metabolomics profiles. [20,40,41] To analyze our data, we chose to use IPA.…”

Tian-Huang Formula, a Traditional Chinese Medicinal Prescription, Improves Hepatosteatosis and Glucose Intolerance Targeting AKT-SREBP Nexus in Diet-Induced Obese Rats

“…At week 19, rats were fasted overnight (12 h) and oral glucose tolerance tests (OGTT, 2 g of 50% glucose/kg body weight) were carried out as described by Wang et al [29] with minor modification. Blood samples were collected through the tail vein, and levels of blood glucose were determined by ONETOUCH UltraEasy glucometer (Johnson, USA) before (0 min) and after glucose injection at different time points (15,30,60, and 120 min). e total area under the curve (AUC) was calculated for OGTT.…”

“…Molecular Network Construction Using IPA. Molecular network construction using Ingenuity Pathways Analysis (IPA, QIAGEN, Germany) was carried out as previously described [28,30].…”

“…RT-qPCR (real-time quantitative reverse transcription-polymerase chain reaction) was performed as previously reported [28,30]. Briefly, hepatic total RNA was extracted with RNAiso plus reagent (Takara Biotechnology, Dalian, China) and was reversely transcribed to cDNA using PrimeScript ™ RT kit with gDNA Eraser (Takara Biotechnology, Dalian, China).…”

“…With the above-mentioned 32 key differential metabolites regulated by THF treatment, pathway enrichment analysis and molecular interaction networks construction were carried out using MetaboAnalyst 4.0 (http://www. metaboanalyst.ca) (Figures 4(a) and 4(b)) and Ingenuity Pathway Analysis software (http://www.qiagen.com), respectively [30,32].…”