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.

Unlimited sucrose consumption during adolescence generates a depressive-like phenotype in adulthood

“…Previous studies suggested that the hippocampus is particularly sensitive to high-fat/high-sugar diets especially when the consumption starts during developmental periods [30,[45][46][47]. Highly palatable food affects the structural and functional integrity of the hippocampus [48] and high sucrose consumption activates endoplasmic reticulum stress pathways [47] and modifies synaptic plasticity in the hippocampus [49]. Hippocampus regulates DA neurons located in the ventral tegmental area (VTA) [50].…”

Long-term consumption of sugar-sweetened beverage during the growth period promotes social aggression in adult mice with proinflammatory responses in the brain

“…The metabolic effects of sucrose consumption examined together with a high fat diet might be different from those associated with a normal fat diet57. In addition, the initiating time point in the life cycle and duration of the sucrose challenge might be important contributing factors275663. Animal strain differences might also contribute to the discrepancy as well.…”

<p>Oxidative stress and biochemical markers in prenatally androgenized sheep after neonatal treatment with GnRH agonist</p>

“…Basal glucose was very similar in the three groups, with values of 70.1±12.7, 72.8±8.11, and 70.±11.3 mg/dL in the C, PA, and LA groups, respectively ( Figure 1I). The triglyceride-glucose (TyG) index, a marker of insulin resistance and metabolic syndrome, [25][26][27][28] was not changed between the control (C) and androgenized groups (PA or LA). As shown in Figure 1J, there were no significant differences in TYG index values in the C group (1,362±392), PA group (1,288±244.3), and LA group (1,336±1,206.5).…”