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Liver damage is not reversed during the lean period in diet-induced weight cycling in mice

Authors

  • Sandra Barbosa-da-Silva,

    1. Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil
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  • Natalia C. da Silva,

    1. Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil
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  • Marcia B. Aguila,

    1. Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil
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  • Carlos A. Mandarim-de-Lacerda

    Corresponding author
    1. Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil
    • Correspondence: Professor Carlos A. Mandarim-de-Lacerda, Universidade do Estado do Rio de Janeiro, Centro Biomedico, Instituto de Biologia, Laboratorio de Morfometria, Metabolismo e Doença Cardiovascular. Av. 28 de Setembro 87 fds, 20551-030 Rio de Janeiro, RJ, Brasil. Email: mandarim@uerj.br

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Abstract

Aim

Weight cycling (WC) is frequent in obesity treatment. We evaluated the degree of regression of the liver damage in WC.

Methods

C57BL/6 male mice received standard chow (SC, 10% energy from lipids) or high-fat diet (HF, 60% energy from lipids) for 6 months (SC6 or HF6) or a diet that alternated every 2 months (SC2/HF2/SC2 or HF2/SC2/HF2).

Results

The body mass gain followed the HF intake and induced WC in the animals. The liver alanine aminotransferase, triglyceride and cholesterol levels were higher in the groups receiving the HF diet for any period. The plasma insulin and glucose levels were the highest in the HF6 and HF2/SC2/HF2 groups. Any HF intake increased the liver mass. All the groups had some degree of liver steatosis, with the SC6 group exhibiting the lowest level (∼23% compared with 50–70%). The activated hepatic stellate cells were sparse throughout the liver sections from the HF6 and HF2/SC2/HF2 groups. The lowest sterol regulatory element-binding protein-1c (SREBP-1c) level was detected in the SC6 group. The peroxisome proliferator-activated receptor (PPAR)-α expression was higher in the SC6 and SC2/HF2/SC2 groups than in the HF6 and HF2/SC2/HF2 groups that showed reduced expression.

Conclusion

WC induced by diet leads to adverse response in the liver, including biochemical and molecular alterations that are not reversed during the lean period of the WC, which must be maintained for a long period to allow the liver to recover from the damage associated with obesity.

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