Dataset Information

Unraveling Hepatic Metabolomic Profiles and Morphological Outcomes in a Hybrid Model of NASH in Different Mouse Strains.

ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) encompasses nonalcoholic steatohepatitis (NASH) and affects 25% of the global population. Although a plethora of experimental models for studying NASH have been proposed, still scarce findings regarding the hepatic metabolomic/molecular profile. In the present study, we sought to unravel the hepatic metabolomic profile of mice subjected to a hybrid model of NASH, by combining a Western diet and carbon tetrachloride administration, for 8 weeks, in male C57BL/6J and BALB/c mice. In both mouse strains, the main traits of NASH-metabolic (glucose intolerance profile), morphologic (extensive microvesicular steatosis and fibrosis, lobular inflammation, and adipose tissue-related inflammation/hypertrophy), and molecular (impaired Nrf2/NF-κB pathway dynamics and altered metabolomic profile)-were observed. The hepatic metabolomic profile revealed that the hybrid protocol impaired, in both strains, the abundance of branched chain-aromatic amino acids, carboxylic acids, and glycosyl compounds, that might be linked to the Nrf2 pathway activation. Moreover, we observed a strain-dependent hepatic metabolomic signature, in which the tricarboxylic acid metabolites and pyruvate metabolism were dissimilarly modulated in C57BL/6J and BALB/c mice. Thus, we provide evidence that the strain-dependent hepatic metabolomic profile might be linked to the distinct underlying mechanisms of NASH, also prospecting potential mechanistic insights into the corresponding disease.

SUBMITTER: Bacil GP

PROVIDER: S-EPMC9952348 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Unraveling Hepatic Metabolomic Profiles and Morphological Outcomes in a Hybrid Model of NASH in Different Mouse Strains.

Bacil Gabriel P GP Romualdo Guilherme R GR Piagge Priscila M F D PMFD Cardoso Daniel R DR Vinken Mathieu M Cogliati Bruno B Barbisan Luís F LF

Antioxidants (Basel, Switzerland) 20230127 2

Nonalcoholic fatty liver disease (NAFLD) encompasses nonalcoholic steatohepatitis (NASH) and affects 25% of the global population. Although a plethora of experimental models for studying NASH have been proposed, still scarce findings regarding the hepatic metabolomic/molecular profile. In the present study, we sought to unravel the hepatic metabolomic profile of mice subjected to a hybrid model of NASH, by combining a Western diet and carbon tetrachloride administration, for 8 weeks, in male C57 ...[more]

PMID: 36829849

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Project description:Endurance racing places high demands on energy metabolism pathways. Metabolomics can be used to investigate biochemical responses to endurance exercise in humans, laboratory animals, and horses. Although endurance horses have previously been assessed in the field (i.e., during races) using broad-window Nuclear Magnetic Resonance metabolomics, these studies included several different race locations, race distances, age classes, and race statuses (finisher or elimination). The present NMR metabolomics study focused on 40 endurance horses racing in three race categories over 90, 120, or 160 km. The three races took place in the same location. Given that energy metabolism is closely related to exercise intensity and duration (and therefore distance covered), the study's objective was to determine whether the metabolic pathways recruited during the race varied as a function of the total ride distance. For each horse, a plasma sample was collected the day before the race, and another was collected at the end of the race. Sixteen, 15, and 9 horses raced over 90, 120, and 160 km, respectively. Proton NMR spectra (500 MHz) were acquired for these 80 plasma samples. After processing, the spectra were divided into bins representing the NMR variables and then classified using orthogonal projection on latent structure models supervised by the sampling time (pre- or post-race) or the distance covered. The models revealed that the post-race metabolomic profiles are associated to the total ride distance groups. By combining biochemical assay results and NMR data in multiblock models, we further showed that enzymatic activities and metabolites are significantly associated to the race category. In the highest race category (160 km), there appears to be a metabolic switch from carbohydrate consumption to lipid consumption in order to maintain glycaemia. Furthermore, signs of protein breakdown were more apparent in the longest race category. The metabolic shift seen in the different racing categories could be related to a mixture of three important factors that are the ride distance, the training status and the inherited endurance capacity of the various horses competing.

Dataset Information

Unraveling Hepatic Metabolomic Profiles and Morphological Outcomes in a Hybrid Model of NASH in Different Mouse Strains.

Publications

Unraveling Hepatic Metabolomic Profiles and Morphological Outcomes in a Hybrid Model of NASH in Different Mouse Strains.

Similar Datasets

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