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Early and sustained exposure to high-sucrose diet triggers hippocampal ER stress in young rats

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Abstract

Early-life environmental insults have been shown to promote long-term development of chronic non-communicable diseases, including metabolic disturbances and mental illnesses. As such, premature consumption of high-sugar foods has been associated to early onset of detrimental outcomes, whereas underlying mechanisms are still poorly understood. In the present study, we sought to investigate whether early and sustained exposure to high-sucrose diet promotes metabolic disturbances that ultimately might anticipate neurological injuries. At postnatal day 21, weaned male rats started to be fed a standard chow (10 % sucrose, CTR) or a high-sucrose diet (25 % sucrose, HSD) for 9 weeks prior to euthanasia at postnatal day 90. HSD did not alter weight gain and feed efficiency between groups, but increased visceral, non-visceral and brown adipose tissue accumulation. HSD rats demonstrated elevated blood glucose levels in both fasting and fed states, which were associated to impaired glucose tolerance. Peripheral insulin sensitivity did not change, whereas hepatic insulin resistance was supported by increased serum triglyceride levels, as well as higher TyG index values. Assessment of hippocampal gene expression showed endoplasmic reticulum (ER) stress pathways were activated in HSD rats, as compared to CTR. HSD rats had overexpression of unfolded protein response sensors, PERK and ATF6; ER chaperone, PDIA2 and apoptosis-related genes, CHOP and Caspase 3; but decreased expression of chaperone GRP78. Finally, HSD rats demonstrated impaired neuromuscular function and anxious behavior, but preserved cognitive parameters. In conclusion, our data indicate that early exposure to HSD promote metabolic disturbances, which disrupt hippocampus homeostasis and might precociously affect its neurobehavioral functions.

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Acknowledgments

Authors are thankful to the LeFisio’s staff for all the technical support during experimental procedures, especially to Caroline Vale, Danylo Noleto and Pâmela Santos. This work was funded by Fundação de Amparo à Pesquisa e ao Desenvolvimento Científico e Tecnológico do Maranhão – FAPEMA through the grants PAEDT-00380/14, UNIVERSAL-00523/14, and UNIVERSAL-00792/14. TMM received fellowship from Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq.

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Authors and Affiliations

  1. Laboratory of Experimental Physiology, Department of Physiological Sciences, Federal University of Maranhão, São Luís, Maranhão, Brazil

    Bruno Araújo Serra Pinto, Thamys Marinho Melo, Karla Frida Torres Flister, Lucas Martins França & Antonio Marcus de Andrade Paes

  2. Laboratory of Vascular Biology, Heart Institute of the School of Medicine, University of São Paulo, São Paulo, São Paulo, Brazil

    Daniela Kajihara, Leonardo Yuji Tanaka & Francisco Rafael Martins Laurindo

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  1. Bruno Araújo Serra Pinto
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  2. Thamys Marinho Melo
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Correspondence to Antonio Marcus de Andrade Paes.

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Pinto, B.A.S., Melo, T.M., Flister, K.F.T. et al. Early and sustained exposure to high-sucrose diet triggers hippocampal ER stress in young rats. Metab Brain Dis 31, 917–927 (2016). https://doi.org/10.1007/s11011-016-9830-1

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