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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Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) particularly among chronic consumers of added sugar-rich diets. However, the impact of early consumption of such diets on NAFLD onset and progression is unclear. Thus, this study sought to characterise metabolic factors involved in NAFLD progression in young mice fed with a high-sucrose diet (HSD). Male Swiss mice were fed HSD or regular chow (CTR) from weaning for up to 60 or 90 days. Obesity development, glucose homeostasis and serum biochemical parameters were determined at each time-point. At day 90, mice were euthanised and white adipose tissue (WAT) collected for lipolytic function assessment and liver for histology, gene expression and cytokines quantification. At day 60, HSD mice presented increased body mass, hypertriglyceridemia, peripheral insulin resistance (IR) and simple steatosis. Upon 90 days on diet, WAT from HSD mice displayed impaired insulin sensitivity, which coincided with increased fasting levels of glucose and free fatty acids (FFA), as well as NAFLD progression to NASH. Transcriptional levels of lipogenic genes, particularly stearoyl-CoA desaturase-1, were consistently increased, leading to hepatic leukocyte infiltration and pro-inflammatory cytokines spillover. Therefore, our dataset supports IR triggering in the WAT as a major factor for dysfunctional release of FFA towards portal circulation and consequent upregulation of lipogenic genes and hepatic inflammatory onset, which decisively concurred for NAFLD-to-NASH progression in young HSD-fed mice. Notwithstanding, this study forewarns against the early introduction of dietary sugars in infant diet, particularly following breastfeeding cessation.

BackgroundMetabolic syndrome (MS)‐related conditions promotes endoplasmic reticulum stress (ERS) in order to control their deleterious effects through activation of adaptive responses known as Unfolded Protein Response (UPR). However, under chronic stress, UPR can evolve to apoptotic pathways. Previously, we have shown that MS induced by high‐sucrose diet triggers the ERS and apoptotic pathways in hippocampus and lead to motor and behavioral impairments in young rats.AimsIn the present study we sought to investigate if sustained exposure to such diet is capable to intensify those metabolic disturbances and anticipate neurological impairments in adult rats.MethodsThus, weaned Wistar rats were divided in two groups: the control group (CTR, n=7), fed with a standard chow; and obese group (HSD, n=7), fed with high‐sucrose diet (25% sucrose). Both groups were followed for 6 months and evaluated for MS development; serum redox profile; and hippocampal gene and protein expressions of UPR sensors (IRE1α, PERK and ATF6), chaperones (GRP78, GRP94, PDI, calnexin and calreticulin), neural plasticity marker (BDNF), antioxidant defense (NRF2), senescence (P53 and P21) and apoptosis (BCL2, CHOP and PARP‐1). Furthermore, cognitive, behavioral and motor functions were also assessed, through Morris water maze, open field and rotarod test, respectively. For aging control, 20 month‐old rats (OLD, n=7) fed with standard chow were included as an aging control for gene/protein expressions and neurological assessments.ResultsThe exposure to high‐sucrose diet was capable to induce MS with marked weight gain, central obesity, dysglicemia in both fasting and fed states, hypertriglyceridemia and high free fatty acids, fat storage in liver, glucose intolerance, hyperinsulinemia and peripheral as well as hepatic insulin resistance. The redox profile assessment showed higher lipid peroxidation with increased serum MDA levels and higher SOD activity in HSD as compared to CTR, but catalase was unchanged. UPR sensors gene expression was reduced in both HSD and OLD groups. All chaperones evaluated presented decreased gene expression, but only GRP78 and GRP94 also presented a decreased protein expression. BDNF expression was reduced in HSD (FC 0.3) and OLD groups, but NRF2 did not present any difference. As expected, the senescence markers were increased in OLD group, but only P21 was increased in HSD (FC 1.8). Assessment of apoptotic pathways showed decreased expression of BCL2 and increased gene and protein expression of CHOP. Assessment of PARP‐1 protein expression suggested the presence of calpain, a necrosis marker. Neurological evaluation demonstrated motor deficit, anxiogenic behavior and cognitive impairments (learning and spatial memory) in HSD.ConclusionsIn to to, our data support that sustained exposure to high‐sucrose diet promotes metabolic disturbances, which disrupt hippocampus homeostasis and lead to cognitive and motor impairments in 6‐months old rats.Support or Funding InformationFundação de Amparo à Pesquisa e ao Desenvolvimento Científico e Tecnológico do Maranhão – FAPEMA and rede INCT Redoxoma

Chronic non-communicable diseases are growing global health problems. The objective of this study was to promote pharmaceutical care for a patient with multimorbidities in order to improve its quality of life. A pharmacotherapeutic follow-up was performed using the SOAP method, registered in the form of clinical evolution, along with laboratory tests, anthropometric measurements and application of validated instruments to assess pharmacological adherence, mental health and quality of life. The report deals with a female patient, 55 years old, obese and dyslipidemic, sedentary, hypertensive, diabetic and on the control phase of breast cancer. Self-medication with antibiotics and a proton pump inhibitor was identified. Despite the good pharmacological adherence, the patient had decompensated diabetes, accompanied by dyslipidemia without treatment and interruption of supplements. After pharmacological and non-pharmacological interventions, the patient showed a significant improvement in the reduction of anthropometric measurements and in biochemical parameters. At the end of the follow-up, pharmaceutical care proved to be fundamental in identifying the patient's health problems, contributing to obtain a more rational pharmacotherapy.