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Taurine supplementation preserves hypothalamic leptin action in normal and protein-restricted mice fed on a high-fat diet

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Abstract

Malnutrition programs the neuroendocrine axis by disruption of food-intake control, leading to obesity. Taurine (Tau) is neuroprotective and improves anorexigenic actions in the hypothalamus. We evaluated the hypothalamic gene-expression profile and food-intake control in protein-restricted mice submitted to a high-fat diet (HFD) and Tau supplementation. Mice were fed on a control (14 % protein—C) or a protein-restricted diet (6 % protein—R) for 6 weeks. Thereafter, mice received, or not, HFD for 8 weeks (CH and RH) with or without 5 % Tau supplementation (CHT and RHT). Protein restriction led to higher food intake, but calories were matched to controls. Excessive calorie intake occurred in HFD mice and this was prevented by Tau supplementation only in the CH group. Additionally, RH and CH mice developed hypothalamic leptin resistance, which was prevented by Tau. Global alterations in the expressions of genes involved in hypothalamic metabolism, cellular defense, apoptosis and endoplasmic reticulum stress pathways were induced by dietary manipulations and Tau treatment. The orexigenic peptides NPY and AgRP were increased by protein restriction and lowered by the HFD. The anorexigenic peptide Pomc was increased by HFD, and this was prevented by Tau only in CH mice. Thus, food intake was disrupted by dietary protein restriction and obesity. HFD-induced alterations were not enhanced by previous protein deficiency, but the some beneficial effects of Tau supplementation upon food intake were blunted by protein restriction. Tau effects upon feeding behavior control are complex and involve interactions with a vast gene network, preventing hypothalamic leptin resistance.

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Acknowledgments

This study was supported by grants from the following Brazilian foundations: Conselho Nacional para o Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP). We thank Prof. Dr. Iscia Lopes-Cendes, Alexandre H. Matos, and Cristiane S. Rocha from Laboratório de Genética Molecular (Faculdade de Ciências Médicas, UNICAMP) for their help in the microarray procedure and data analysis. We also thank Maria E.R. Camargo and Prof. Dr. Jörg Kobarg from Brazilian Synchrotron Light Laboratory for help and technical assistance in the manipulation of microarray chips, and Nicola Conran for editing the English.

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All contributing authors report no conflicts of interest.

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Camargo, R.L., Batista, T.M., Ribeiro, R.A. et al. Taurine supplementation preserves hypothalamic leptin action in normal and protein-restricted mice fed on a high-fat diet. Amino Acids 47, 2419–2435 (2015). https://doi.org/10.1007/s00726-015-2035-9

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