title: Early and sustained exposure to high-sucrose diet triggers hippocampal ER stress in young rats.
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.
authors.affiliation: Laboratory of Experimental Physiology, Department of Physiological Sciences, Federal University of Maranhão, São Luís, Maranhão, Brazil.
authors.forename: Bruno Araújo Serra
authors.initials: BA
authors.lastname: Pinto
authors.affiliation: Laboratory of Experimental Physiology, Department of Physiological Sciences, Federal University of Maranhão, São Luís, Maranhão, Brazil.
authors.forename: Thamys Marinho
authors.initials: TM
authors.lastname: Melo
authors.affiliation: Laboratory of Experimental Physiology, Department of Physiological Sciences, Federal University of Maranhão, São Luís, Maranhão, Brazil.
authors.forename: Karla Frida Torres
authors.initials: KF
authors.lastname: Flister
authors.affiliation: Laboratory of Experimental Physiology, Department of Physiological Sciences, Federal University of Maranhão, São Luís, Maranhão, Brazil.
authors.forename: Lucas Martins
authors.initials: LM
authors.lastname: França
authors.affiliation: Laboratory of Vascular Biology, Heart Institute of the School of Medicine, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Daniela
authors.initials: D
authors.lastname: Kajihara
authors.affiliation: Laboratory of Vascular Biology, Heart Institute of the School of Medicine, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Leonardo Yuji
authors.initials: LY
authors.lastname: Tanaka
authors.affiliation: Laboratory of Vascular Biology, Heart Institute of the School of Medicine, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Francisco Rafael Martins
authors.initials: FR
authors.lastname: Laurindo
authors.affiliation: Laboratory of Experimental Physiology, Department of Physiological Sciences, Federal University of Maranhão, São Luís, Maranhão, Brazil. marcuspaes@ufma.br.
authors.forename: Antonio Marcus de Andrade
authors.initials: AM
authors.lastname: Paes
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects*; D019422:Dietary Sucrose / Q000008:administration & dosage*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000378:metabolism
chemical_list: D019422:Dietary Sucrose; D014280:Triglycerides; D005947:Glucose
keywords: Developmental origins of health and disease; High-sucrose diet; Hippocampus; Metabolic syndrome; Neurological impairment; Unfolded protein response