Impact of High-Fat Diet-induced Metabolic Dysfunction-associated Steatotic Liver Disease on Heart, Kidney, and Skeletal Muscle Metabolomes in Wild-Type Mice

resumo

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) can be recapitulated in mice fed a high-fat diet. The development of MASLD and the diet per se can both perturb metabolism in key extrahepatic tissues such as the heart, kidney, and skeletal muscle. To date, these alterations have not been well described in this animal model of diet-induced MASLD. Methodology: Male C57BL/6J mice were fed either standard (SC, n = 12) or high-fat chow (HF, n = 11) for 18 weeks. Metabolites were extracted from the heart, kidney, and skeletal muscle and analyzed by 1H nuclear magnetic resonance (NMR) spectroscopy, along with multivariate and univariate statistical analyses. Results: Kidney metabolite profiles exhibited the largest differences between HF and SC diets, followed by those of skeletal muscle and then the heart. Some alterations were common across all tissues, namely decreased trimethylamine and elevated levels of linoleic acid and polyunsaturated fatty acids in HF compared to SC (p < 0.05 for all three metabolites). Overall, the metabolite variations were consistent with shifts in carbohydrate and lipid substrate selection for oxidation, increased tissue stress in the heart and kidneys, and altered choline metabolism. These findings may serve as additional important descriptors of MASLD onset and progression.

palavras-chave

MAGNETIC-RESONANCE-SPECTROSCOPY; DE-NOVO LIPOGENESIS; INSULIN-RESISTANCE; TRIGLYCERIDE CONTENT; HUMANS; NAFLD; CARDIOPROTECTION; CARBOHYDRATE; PATHOGENESIS; MODULATION

categoria

Biochemistry & Molecular Biology

autores

Silva, JG; Tavares, L; Belew, GD; Rodrigues, JA; Araújo, R; Gil, AM; Jones, JG

Grupos

G5 - Materiais Biomiméticos, Biológicos e Vivos

Projectos

CICECO - Aveiro Institute of Materials (UIDB/50011/2020)

CICECO - Aveiro Institute of Materials (UIDP/50011/2020)

Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)

Rede Nacional de Ressonância Magnética Nuclear (PTNMR)

agradecimentos

The authors thank Tatiana Carneiro, Daniela Bispo, and Daniela Duarte (University of Aveiro, Aveiro, Portugal), as well as Mariana Palma and Ivan Viegas (University of Coimbra, Coimbra, Portugal) for their help and guidance. This work was financed by the European Regional Development Fund (ERDF) through the Centro 2020 Regional Operational Program under project FCT-FEDER-02/SAICT/2017/028147 and through the COMPETE 2020-Operational Program for Competitiveness and Internationalisation and Portuguese national funds via FCT-Fundacao para a Ciencia e a Tecnologia, within the scope of the projects CIBB-Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, grants PTDC/BIA-BQM/28147/2017, PTDC/BAA-AGR/3550/2020, UIDB/04539/2020, UIDP/04539/2020, and LA/P/0058/2020, and CICECO-Aveiro Institute of Materials, University of Aveiro, grants UIDB/50011/2020 (doi: 10.54499/UIDB/50011/2020), UIDP/50011/2020 (doi: 10.54499/UIDP/50011/2020), and LA/P/0006/2020 (doi: 10.54499/LA/P/0006/2020). The NMR spectrometer is part of the National NMR Network (PTNMR) and is partially supported by Infrastructure Project No 022161 (cofinanced by FEDER through COMPETE 2020, POCI, and PORL, and FCT through PIDDAC). J.G.S. is supported by a PhD grant through CIBB and financed by FCT (UIDB/154022/2022).