Integrated omics analysis for characterization of the contribution of high fructose corn syrup to non-alcoholic fatty liver disease in obesity

Papadopoulos, Grigorios; Legaki, Aigli‐Ioanna; Georgila, Konstantina; Vorkas, Panagiotis A.; Giannousi, Eirini; Stamatakis, George; Moustakas, Ioannis I; Petrocheilou, Maria; Pyrina, Iryna; Gercken, Bettina; Kassi, Eva; Chavakis, Triantafyllos; Pateras, Ioannis S.; Panayotou, George; Gika, Helen; Samiotaki, Martina; Eliopoulos, Aristides G.; Chatzigeorgiou, Antonios

doi:10.1016/j.metabol.2023.155552

Cited by 10 publications

(4 citation statements)

References 58 publications

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“… 31 , 32 It was found that hyperactivation of the tricarboxylic acid cycle in high-fructose corn syrup-fed mice may contribute to the exacerbation of steatosis during HFD-HFCS-induced NAFLD. 33 TCA cycle dysregulation was also observed in high-fat diet mice. 34 Hyperactivation of the TCA cycle after the HFDHFr diet in the present study was reversed after OMT intervention, suggesting that OMT may ameliorate NAFLD by reverting to the pathway of dysregulated TCA cycle metabolism.…”

Section: Discussionmentioning

confidence: 91%

Oxymatrine Alleviates High-Fat-High-Fructose-Induced Fatty Liver in Rats: Understanding the Molecular Mechanism Through an Untargeted Metabonomics Study

Li,

Wang,

Wang

et al. 2023

DMSO

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Objective Previous studies have shown that oxymatrine (OMT) can improve high-fat-high-fructose-diet-induced non-alcoholic fatty liver disease (NAFLD), and our study aimed to explore its possible metabolic potential mechanisms. Methods Wistar rats were fed a high-fat-high-fructose diet for 8 weeks and treated with oxymatrine by gavage for the last 4 weeks. We measured biochemical indicators and pathological changes in each group and used liquid chromatography-mass spectrometry (LC-MS) to analyze changes in metabolites in the serum and liver of the rats. Results The results showed that OMT can alleviate the high-fat-high-fructose-induced weight gain and hepatic lipid deposition in rats. Metabolomic analysis showed that the level of eicosapentaenoic acid (EPA) was downregulated and levels of desmosterol and d-galactose were upregulated in livers fed with HFDHFr. The levels of L-isoleucine, L-valine, arachidonic acid (AA), taurocholic acid (TCA), chenodeoxycholyltaurine (TDCA), isocitrate, and glutathione (GSH) were downregulated in the liver, whereas those of linoleic acid (LA), phosphocholine (PC), glycerophosphocholine (GPC), and oxidized glutathione (GSSG) were upregulated in the serum treated with OMT. Conclusion In summary, OMT can improve HFDHFr-induced NAFLD, and metabolomic analysis can provide an early warning for the development of NAFLD as well as provide a rationale for therapeutic targets.

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Section: Discussionmentioning

confidence: 91%

Oxymatrine Alleviates High-Fat-High-Fructose-Induced Fatty Liver in Rats: Understanding the Molecular Mechanism Through an Untargeted Metabonomics Study

Li,

Wang,

Wang

et al. 2023

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“…Natural fructose obtained from plants typically confers metabolic benefits due to its slower absorption rate and the presence of beneficial plant fiber and antioxidants. In contrast, industrial fructose sources such as HFCS and sucrose, particularly in liquid form, are rapidly absorbed and implicated in hepatic IR and MASLD 43 - 45 . Notably, HFCS-rich drinks nearly triple the likelihood of developing MASLD 7 .…”

Section: Discussionmentioning

confidence: 99%

High dietary Fructose Drives Metabolic Dysfunction-Associated Steatotic Liver Disease via Activating ubiquitin-specific peptidase 2/11β-hydroxysteroid dehydrogenase type 1 Pathway in Mice

Li,

Sheng

et al. 2024

Int. J. Biol. Sci.

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Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of chronic liver-related morbidity and mortality. Though high fructose intake is acknowledged as a metabolic hazard, its role in the etiology of MASLD requires further clarification. Here, we demonstrated that high dietary fructose drives MASLD development and promotes MASLD progression in mice, and identified Usp2 as a fructose-responsive gene in the liver. Elevated USP2 levels were detected in the hepatocytes of MASLD mice; a similar increase was observed following fructose exposure in primary hepatocytes and mouse AML12 cells. Notably, hepatocytes overexpressing USP2 presented with exaggerated lipid accumulation and metabolic inflammation when exposed to fructose. Conversely, USP2 knockdown mitigated these fructose-induced changes. Furthermore, USP2 was found to activate the C/EBPα/11β-HSD1 signaling, which further impacted the equilibrium of cortisol and cortisone in the circulation of mice. Collectively, our findings revealed the role of dietary fructose in MASLD pathogenesis and identified the USP2-mediated C/EBPα/ 11β-HSD1 signaling as a potential target for the management of MASLD.

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“…During the MASLD-to-MASH transition, the liver’s innate immune compartment is triggered via de novo lipogenesis-driven lipotoxic steatosis ( Papadopoulos et al, 2023 ) and aberrant peroxidation of fatty metabolic intermediates ( Seki et al, 2002 ). Concurrently, the liver microenvironment is changing dramatically; oxidative damage ( Feldstein et al, 2003 ; Zhang et al, 2022b ) and the number of senescent hepatocytes increase gradually ( Papatheodoridi et al, 2020 ), while inflammatory cues (i.e., damage-associated molecular patterns, DAMPs) alter the liver’s microenvironment to foster disease progression and tissue damage.…”

Section: Introductionmentioning

confidence: 99%

Τ cell-mediated adaptive immunity in the transition from metabolic dysfunction-associated steatohepatitis to hepatocellular carcinoma

Papadopoulos,

Giannousi,

Avdi

et al. 2024

Front. Cell Dev. Biol.

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Metabolic dysfunction-associated steatohepatitis (MASH) is the progressed version of metabolic dysfunction-associated steatotic liver disease (MASLD) characterized by inflammation and fibrosis, but also a pathophysiological “hub” that favors the emergence of liver malignancies. Current research efforts aim to identify risk factors, discover disease biomarkers, and aid patient stratification in the context of MASH-induced hepatocellular carcinoma (HCC), the most prevalent cancer among MASLD patients. To investigate the tumorigenic transition in MASH-induced HCC, researchers predominantly exploit preclinical animal-based MASH models and studies based on archived human biopsies and clinical trials. Recapitulating the immune response during tumor development and progression is vital to obtain mechanistic insights into MASH-induced HCC. Notably, the advanced complexity behind MASLD and MASH pathogenesis shifted the research focus towards innate immunity, a fundamental element of the hepatic immune niche that is usually altered robustly in the course of liver disease. During the last few years, however, there has been an increasing interest for deciphering the role of adaptive immunity in MASH-induced HCC, particularly regarding the functions of the various T cell populations. To effectively understand the specific role of T cells in MASH-induced HCC development, scientists should urgently fill the current knowledge gaps in this field. Pinpointing the metabolic signature, sketching the immune landscape, and characterizing the cellular interactions and dynamics of the specific T cells within the MASH-HCC liver are essential to unravel the mechanisms that adaptive immunity exploits to enable the emergence and progression of this cancer. To this end, our review aims to summarize the current state of research regarding the T cell functions linked to MASH-induced HCC.

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Integrated omics analysis for characterization of the contribution of high fructose corn syrup to non-alcoholic fatty liver disease in obesity

Cited by 10 publications

References 58 publications

Oxymatrine Alleviates High-Fat-High-Fructose-Induced Fatty Liver in Rats: Understanding the Molecular Mechanism Through an Untargeted Metabonomics Study

Oxymatrine Alleviates High-Fat-High-Fructose-Induced Fatty Liver in Rats: Understanding the Molecular Mechanism Through an Untargeted Metabonomics Study

High dietary Fructose Drives Metabolic Dysfunction-Associated Steatotic Liver Disease via Activating ubiquitin-specific peptidase 2/11β-hydroxysteroid dehydrogenase type 1 Pathway in Mice

Τ cell-mediated adaptive immunity in the transition from metabolic dysfunction-associated steatohepatitis to hepatocellular carcinoma

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