Júlio Cezar de Oliveira

Malnutrition during adolescence can cause metabolic diseases later in life. This study examined the short- and long-term effects of undernutrition during adolescence on body composition, glucose homeostasis and redox balance. Male (n = 32) and female (n = 32) Wistar rats were fed a rodent chow reduced by 50% (FR50) of the amount consumed by control rats (CONT) from 30 to 60 days and then fed ad libitum until 120 days of age. Half of the rats were euthanized at 60 and the other half at 120 days old. At 60 and 120 days old, glucose and insulin tolerance test; skeletal muscle, visceral fat, liver and interscapular brown adipose tissue (iBAT) weights; and oxidative stress marker levels in the liver and iBAT were evaluated. The FR50 male (FR50-M) and female (FR50-F) rats exhibited a lean phenotype and high insulin sensitivity at 60 days of age (p < 0.05), but at 120 days of age, they exhibited an obese phenotype with high insulin sensitivity (p < 0.05). An increase in liver GSH was observed as only a short-term effect (p < 0.05). At 120 days of age, only male rats displayed increased iBAT GSH levels (p < 0.05) and reduced CAT activity (p < 0.01). In summary, undernutrition during adolescence affects body composition, glucose homeostasis and redox status equally in males and females but causes long-term impairment of the redox status of iBAT only in male rats.

Both perinatal malnutrition and elevated glucocorticoids are pivotal triggers of the growing global pandemic of metabolic diseases. Here, we studied the effects of metabolic stress responsiveness on glucose–insulin homeostasis and pancreatic-islet function in male Wistar offspring whose mothers underwent protein restriction during lactation. During the first two weeks after delivery, lactating dams were fed a low-protein (4% protein, LP group) or normal-protein diet (22.5% protein, NP group). At 90 days of age, male rat offspring were challenged with food deprivation (72 h of fasting), intracerebroventricular (icv) injection of dexamethasone (2 µL, 2.115 mmol/L) or chronic intraperitoneal injection of dexamethasone (1 mg/kg body weight/5 days). Body weight, food intake, intravenous glucose tolerance test (ivGTT) results, insulin secretion and biochemical parameters were assessed. LP rats did not display significant metabolic changes after long-term starvation (p > 0.05) or under the central effect of dexamethasone (p = 0.999). Chronic dexamethasone induced rapid hyperglycemia (~1.2-fold, p < 0.001) and hyperinsulinemia (NP: 65%; LP: 216%; p < 0.001), decreased insulin sensitivity (NP: ~2-fold; LP: ~4-fold; p < 0.001), reduced insulinemia (20%) and increased glycemia (35%) only in NP rats under ivGTT conditions (p < 0.001). Glucose and acetylcholine insulinotropic effects, as well as the muscarinic receptor antagonist response, were reduced by chronic dexamethasone only in pancreatic islets from NP rats (p < 0.05). The direct effect of dexamethasone on pancreatic islets reduced insulin secretion (NP: 60.2%, p < 0.001; LP: 33.8%, p < 0.001). Peripheral glucose–insulin dyshomeostasis and functional failure of pancreatic islets in LP rats, as evidenced by an impaired acute and chronic response to metabolic stress, may be due to excessive corticosterone action as a long-term consequence.

The progressive increase in the number of deaths caused by Alzheimer’s disease (AD) in Brazil and around the world between 2010 and 2020 raises questions in scientific society. At the same time, there is also an increase in life expectancy at birth (LEB). Thus, the aim of this study was, for the first time, to compare the increase in AD mortality rate (ADMR) in Brazilian regions over the years 2010 to 2020 with the increase in LEB, and investigate the possible correlation between these demographic transition phenomena and pesticide sales and exposure during this period. Data were extracted from the Brazilian Institute of Geography and Statistics (IBGE), from the Department of Informatics and Technology of the Brazilian Ministry of Health (DATASUS) and from the Brazilian Institute of the Environment and Renewable Natural Resources (IBAMA). There was a significant increase in life expectancy at birth and in ADMR over the years between 2010 and 2020 in all Brazilian regions, with the female population in the South region being the most affected. In conclusion, there is a strong positive correlation between the increase in ADMR and LEB; ADMR and Human Development Index (HDI) and ADMR and pesticide sales and exposure in Brazil over the years studied.

Maternal obesity may trigger long-term neurodevelopmental disorders in offspring. Considering the benefits of the Brazil nut (Bertholletia excelsa H.B.K.), a rich source of nutrients such as selenium, this study aimed to evaluate its effect on the behavior of obese rat offspring and its relationship with oxidative stress. From 60 days of age until weaning, female Wistar rats were fed a high-fat diet (mHF) or an HF diet supplemented with 5% Brazil nut (mHF/BN), while control mothers (mCTL) were fed a standard diet or a standard diet supplemented with 5% Brazil nut (mBN). Male pups received a standard diet throughout life and, at 30 and 90 days old, were subjected to behavioral tasks to evaluate anxiety and cognition. Biochemical evaluations were performed at 90 days of age. No alterations were observed in the anxiety behavior of the offspring. However, the offspring of the mHF group (oHF) exhibited impaired short-term memory at 30 and 90 days of age and impaired long-term memory at 30 days. Short-term memory impairment was prevented by Brazil nuts in young rats (30 days). While the serum selenium concentration was reduced in the oHF group, the serum catalase concentration was reduced in all groups, without changes in lipid peroxidation or protein carbonylation. Brazil nut maternal diet supplementation prevented short- and long-term cognitive impairment in the offspring, which may be related to the selenium levels.

Introdução: A obesidade é considerada um dos maiores problemas de saúde pública na atualidade, pois, além de sua relevância epidemiológica, pode trazer inúmeras consequências graves ao indivíduo. Adem

Introdução: A metformina é amplamente usada na clínica médica como a primeira escolha no tratamento de doenças, tais como o diabetes mellitus tipo 2, em paralelo, sabe-se que seu uso também pode causa

Herein, we assessed milk hormones, the biochemical composition of milk, and its association with neonatal body weight gain and metabolic homeostasis in weaned rats whose mothers were undernourished in the last third of pregnancy. From the 14th day of pregnancy until delivery, undernourished mothers had their food restricted by 50% (FR50), whereas control mothers were fed ad libitum. The litter size was adjusted to eight pups, and rats were weaned at 22 days old. Milk and blood from mothers, as well as blood and tissues from pups, were collected for further analyses. At birth, FR50 pups were smaller than control pups, and they exhibited hyperphagia and rapid catch-up growth during the suckling period. On day 12, the milk from FR50 mothers had higher energy content, glucose, total cholesterol, triglycerides, and acylated ghrelin but lower leptin and corticosterone levels. Interestingly, FR50 mothers were hypoglycemic and hyperleptinemic at the end of the nursing period. Weaned FR50 pups had an obese phenotype and exhibited insulin resistance, which was associated with hyperglycemia and hypertriglyceridemia; they also had high blood levels of total cholesterol, leptin, and acylated ghrelin. In addition, the protein expression of growth hormone secretagogue receptor (GHSR) in the hypothalamus was increased by almost 4-fold in FR50 pups. In summary, maternal calorie restriction during the last third of pregnancy disrupts energy and metabolic hormones in milk, induces pup hyperleptinemia and hyperghrelinemia, and upregulates their hypothalamic GHSR, thus suggesting that the hypothalamic neuroendocrine circuitry may be working to address the early onset of obesity.