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Early unhealthy eating habits underlie morpho-functional changes in the liver and adipose tissue in male rats

Abstract

Early-life consumption of high-fat and sugar-rich foods is recognized as a major contributor for the onset of metabolic dysfunction and its related disorders, including diabetes and nonalcoholic fatty liver disease. The lifelong impact of early unhealthy eating habits that start at younger ages remains unclear. Therefore, to better understand the effects of diet, it is essential to evaluate the structural and functional changes induced in metabolic organs and potential mechanisms underlying those changes. To investigate the long-term effects of eating habits, young male rats were exposed to high-sugar and high-energy diets. After 14 weeks, body composition was assessed, and histopathological changes were analyzed in the liver and adipose tissue. Serum biochemical parameters were also determined. Expression of inflammatory markers in the liver was evaluated by immunohistochemistry. Our results revealed that serum levels of glucose, creatinine, aspartate transaminase (AST), alanine transaminase (ALT), and lipid profile were increased in rats red high-sugar and high-energy diets. Histopathological alterations were observed, including abnormal hepatocyte organization and lipid droplet accumulation in the liver, and abnormal structure of adipocytes. In both unhealthy diet groups, hepatic expression of Toll-like receptor 4 (TLR4), cyclooxygenase 2 (COX-2), and E-selectin were increased, as well as a biomarker of oxidative stress. Together, our data demonstrated that unhealthy diets induced functional and structural changes in the metabolic organs, suggesting that proinflammatory and oxidative stress mechanisms trigger the hepatic alterations and metabolic dysfunction.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This work was supported by ERDF through the operation POCI-01-0145-FEDER-007746 funded by the Programa Operacional Competitividade e Internacionalização—COMPETE2020 and by National Funds through FCT—Fundação para a Ciência e a Tecnologia, I.P., within CINTESIS, R&D Unit (reference UIDB/4255/2020). This work is financed by national funds from FCT—Fundação para a Ciência e a Tecnologia, I.P., in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences—UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB. Sandra Leal was supported by a research grant from CESPU-IINFACTS [grant number FoodMicrobiome_CESPU_2017].

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Contributions

SN contributed with laboratory work, data analysis and interpretation, preparation of the figures and the manuscript. BMF contributed with data analysis and interpretation and revising the manuscript. RS contributed with data analysis and interpretation and revising the manuscript. SL contributed to the conception and preparation of the study, data analysis and interpretation, and revising the manuscript. FG and LCM contributed with laboratory work and data analysis. AC contributed to the conception of the experimental model and revising the manuscript. SIS contributed with the conception and preparation of the study, laboratory work, data analysis and interpretation and revising the manuscript. All authors approved the final version of the manuscript.

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Correspondence to Bruno M. Fonseca.

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The authors declare no conflicts of interest.

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Nogueira, S., Garcez, F., Sá, S. et al. Early unhealthy eating habits underlie morpho-functional changes in the liver and adipose tissue in male rats. Histochem Cell Biol 157, 657–669 (2022). https://doi.org/10.1007/s00418-022-02092-2

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  • DOI: https://doi.org/10.1007/s00418-022-02092-2

Keywords

  • High-energy diet
  • High-sugar diet
  • Young rat model
  • Metabolic dysfunction
  • Immunohistochemistry
  • Histomorphometric study