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Oral supplementations with l-glutamine or l-alanyl-l-glutamine do not change metabolic alterations induced by long-term high-fat diet in the B6.129F2/J mouse model of insulin resistance

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Abstract

In this work, we aimed to investigate the effects of long-term supplementations with l-glutamine or l-alanyl-l-glutamine in the high-fat diet (HFD)-fed B6.129SF2/J mouse model over insulin sensitivity response and signaling, oxidative stress markers, metabolism and HSP70 expression. Mice were fed in a standard low-fat diet (STA) or a HFD for 20 weeks. In the 21th week, mice from the HFD group were allocated in five groups and supplemented for additional 8 weeks with different amino acids: HFD control group (HFD-Con), HFD + dipeptide l-alanyl-l-glutamine group (HFD-Dip), HFD + l-alanine group (HFD-Ala), HFD + l-glutamine group (HFD-Gln), or the HFD + l-alanine + l-glutamine (in their free forms) group (HFD-Ala + Gln). HFD induced higher body weight, fat pad, fasted glucose, and total cholesterol in comparison with STA group. Amino acid supplementations did not induce any modifications in these parameters. Although insulin tolerance tests indicated insulin resistance in all HFD groups, amino acid supplementations did not improve insulin sensitivity in the present model. There were also no significant differences in the immunocontents of insulin receptor, Akt, and Toll-like receptor-4. Notably, total 70 kDa heat shock protein (HSP72 + HSP73) contents in the liver was markedly increased in HFD-Con group as compared to STA group, which might suggest that insulin resistance is only in the beginning. Apparently, B6.129SF2/J mice are more resistant to the harmful effects of HFD through a mechanism that may include gut adaptation, reducing the absorption of nutrients, including amino acids, which may explain the lack of improvements in our intervention.

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Acknowledgments

We thank the Federal University of Rio Grande do Sul (UFRGS), Department of Physiology, for supporting this work. This work was partially supported by grants received from the Brazilian National Council for Scientific and Technological Development (CNPq, Grants from MCT/CNPq, MS/DECIT, CT-CIOTEC and CTSaúde, Grants #551097/2007-8, 402626/2012-5 and 402364/2012-0, to PIHBJ; 402398/2013-2 and 372373/2013-5 to MK).

Authors’ contributions

PMB, MK, HKT, and PIHBJ designed the study. PMB and HTS completed all the experiments described in this manuscript. GFH, MAB, MK, GN, LDZN, and MILR were involved in animal manipulation and studies on glycemic control and glutathione status. MK, HTS, GFH, GN, LDZN, and CMS performed molecular studies. PMB, MK, HTS, HKT, and PIHBJ analyzed the results. PMB, MK, and PIHBJ co-wrote the article. PIHBJ provided experimental advice and revised the final version of the manuscript. All the authors had final approval of the submitted and published versions.

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  1. Laboratory of Cellular Physiology, Department of Physiology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento Leite, 500, 2nd floor, suite 350, Porto Alegre, RS, 90050-170, Brazil

    Patricia Martins Bock, Mauricio Krause, Helena Trevisan Schroeder, Gabriela Fernandes Hahn, Hilton Kenji Takahashi, Cinthia Maria Schöler, Graziella Nicoletti, Luiz Domingos Zavarize Neto, Maria Inês Lavina Rodrigues, Maciel Alencar Bruxel & Paulo Ivo Homem de Bittencourt Jr.

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  1. Patricia Martins Bock
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The authors declare no conflict of interest and no competing interests such as consultancies, financial involvement, patent ownership, etc. in relation to the work described herein. CNPq (the funding organism) had no involvement in the propositions presented in this manuscript.

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All the procedures performed in studies involving the animals followed the ethical rules established by Arouca’s Act (Federal Law 11794/2008) and the Guide for Care and Use of Experimental Animals published by the National Institutes of Health (NIH publication no. 85-23, revised in 1996). The procedures were approved by the Federal University of Rio Grande do Sul Ethics Committee on Animal Experimentation (CEUA #21293/2011), according to the guidelines of the Brazilian National Council for the Control of Animal Experimentation (CONCEA).

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Bock, P.M., Krause, M., Schroeder, H.T. et al. Oral supplementations with l-glutamine or l-alanyl-l-glutamine do not change metabolic alterations induced by long-term high-fat diet in the B6.129F2/J mouse model of insulin resistance. Mol Cell Biochem 411, 351–362 (2016). https://doi.org/10.1007/s11010-015-2597-6

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