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Exploring the impact of caloric restriction on molecular mechanisms of liver damage induced by sucrose intake in the drinking water

Published online by Cambridge University Press:  11 November 2024

Morena Wiszniewski Open the ORCID record for Morena Wiszniewski [Opens in a new window] ,
Lilian Caldareri ,
Diego Mori ,
Camila Martinez Calejman ,
Cora B. Cymeryng  and
Esteban M. Repetto
Morena Wiszniewski
Affiliation:
CONICET – Universidad de Buenos Aires. Centro de Estudios Farmacológicos y Botánicos (CEFYBO). Laboratorio de Endocrinología Molecular, Buenos Aires, Argentina Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Bioquímica y Biología Bucal, Buenos Aires, Argentina
Lilian Caldareri
Affiliation:
CONICET – Universidad de Buenos Aires. Centro de Estudios Farmacológicos y Botánicos (CEFYBO). Laboratorio de Endocrinología Molecular, Buenos Aires, Argentina
Diego Mori
Affiliation:
CONICET – Universidad de Buenos Aires. Centro de Estudios Farmacológicos y Botánicos (CEFYBO). Laboratorio de Endocrinología Molecular, Buenos Aires, Argentina
Camila Martinez Calejman
Affiliation:
CONICET – Universidad de Buenos Aires. Centro de Estudios Farmacológicos y Botánicos (CEFYBO). Laboratorio de Endocrinología Molecular, Buenos Aires, Argentina
Cora B. Cymeryng
Affiliation:
CONICET – Universidad de Buenos Aires. Centro de Estudios Farmacológicos y Botánicos (CEFYBO). Laboratorio de Endocrinología Molecular, Buenos Aires, Argentina Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana. Cátedra de Bioquímica Humana I, Buenos Aires, Argentina
Esteban M. Repetto*
Affiliation:
CONICET – Universidad de Buenos Aires. Centro de Estudios Farmacológicos y Botánicos (CEFYBO). Laboratorio de Endocrinología Molecular, Buenos Aires, Argentina Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica. Cátedra de Bioquímica Clínica I, Buenos Aires, Argentina
*
Corresponding author: Esteban M. Repetto; Email: [email protected]
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Abstract

A positive association has been demonstrated between consumption of sucrose-sweetened beverages and the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD). Since the administration of 30 % sucrose in the drinking water (sucrose-rich diet (SRD)) to rats has proven to be a good model of systemic insulin resistance, the aim of our study was to analyse the effect of caloric restriction applied on SRD-treated rats by switching back to a standard diet, on liver morphology, function and metabolism. Consumption of an SRD causes a metabolic shift towards gluconeogenesis and fatty acid synthesis leading to an increase in TAG levels in plasma and in the liver that were associated with a decrease in insulin sensitivity. Moreover, our results show that animals fed an SRD develop steatohepatitis characterised by the generation of oxidative stress, endoplasmic reticulum (ER) stress, inflammation and apoptosis. Although no histological changes were observed after a 2-week caloric restriction, key pathways associated with the progression of MASLD as inflammation, ER stress and apoptosis were slowed down. Notably, this 2-week intervention also increased liver insulin sensitivity (evaluated by AKT activity in this tissue) and drove the lipid metabolic profile towards oxidation, thus lowering circulating TAG levels. In summary, the present study uncovers underlying mechanisms affected, and their metabolic consequences, during the first stages of the phenotypic reversal of steatohepatitis by switching back to a standard diet after receiving sucrose-sweetened water for several weeks.

Keywords

Caloric restrictionSteatohepatitisLiver metabolismInflammationUnfolded protein responseOxidative stress
Type
Research Article
Information
British Journal of Nutrition , Volume 132 , Issue 12 , 28 December 2024 , pp. 1562 - 1574
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Copyright
© The Author(s), 2024. Published by Cambridge University Press on behalf of The Nutrition Society

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