Brazil nut (Bertholletia excelsa H.B.K.) and Brazil nut oil: effects on oxidative stress and potential therapeutic health benefits from human, animal, and cell culture models.

Brazil nut (Bertholletia excelsa H.B.K.) is characterized by its high nutritional and energetic value. It contains high levels of l-arginine, antioxidant vitamins, phenolic compounds, and phytosterols. In addition to their biological functions, bioactive compounds and essential fatty acids present therapeutic effects on chronic disease prevention through their antioxidant effects. Thus, this review aims to present the most recent scientific evidence on the effect of Brazil nut on human health. A search for scientific articles was carried out through the MEDLINE/PubMed, Science Direct, and LILACS databases, considering articles published between the years 2010 and 2023. The results showed that Brazil nuts and Brazil nut oil, when consumed regularly and associated with a balanced diet, can improve lipid profile, attenuate inflammatory response, and improve oxidative stress through increased activity and gene expression of antioxidant enzymes. However, further studies are recommended to better understand the mechanisms of action.

Effects of Supplementation of Murici (Byrsonima crassifolia) and Taperebá (Spondias mombin) Pulp Extracts on Food Intake, Body Parameters, and Oxidative Stress Markers in Healthy Rats.

This study evaluates the effects of supplementation of murici (Byrsonima crassifolia) and taperebá (Spondias mombin) pulp extracts on dietary intake, body composition, biochemical parameters, and markers of oxidative stress. Two experiments were conducted with a total of 80 healthy male Wistar rats and a 30-day supplementation. In the first experiment, animals were divided into control (C) group, murici group 50 mg/(kg⸱day) (50Mu), murici group 100 mg/(kg⸱day) (100Mu), and murici group 200 mg/(kg⸱day) (200Mu). In the second experiment, animals were divided into C group, taperebá group 50 mg/(kg⸱day) (50Tap), taperebá group 100 mg/(kg⸱day) (100Tap), and taperebá group 200 mg/(kg⸱day) (200Tap). Results showed lower feed intake in 50Mu, 100Mu, and 100Tap groups (13%, 12%, and 10%, respectively, P < .05) and lower body fat in 200Mu, 100Tap, and 200Tap groups (16.0%, 29.1%, and 27.1%, respectively, P < .05). Only the 100Tap group showed reduced adipose tissue content (30.4%; P < .05). Increased plasma antioxidant capacity was observed at all doses for both fruits. Taperebá supplementation reduced ferrous oxidation-xylenol orange levels (50Tap: 8.4%, 100Tap: 16.1%, 200Tap: 24.3%; P < .05) and increased thiol levels (50Tap: 39%, 100Tap: 31%; P < .05). Serum thiobarbituric acid reactive substances levels were reduced in all groups receiving taperebá (50Tap: 77.7%, 100Tap: 73.1%, 200Tap: 73.8%; P < .05) and murici (50Mu: 44.5%, 100Mu: 34%, 200Mu: 43%; P < .05). Therefore, it is suggested that the inclusion of these fruits in the diet can contribute to health maintenance and disease prevention, through their effects on controlling food intake, improving body composition, and in combating oxidative stress.

Supplementation of diet with Brazil nut modulates body composition, bone parameters, and lipid peroxidation in Wistar rats.

Oxidative stress, adipose tissue, and bone compartments can be disturbed in chronic diseases. Non-pharmacological strategies, such as Brazil nuts (BNs), can improve these parameters. This study evaluated the effects of BN supplementation at different concentrations on body composition, lipid profile, and peroxidation in healthy rats. Male Wistar rats were divided into three groups: control (CT), Brazil nut 5% (BN5), and Brazil nut 10% (BN10) groups. Body composition, brown adipose tissue (BAT), plasma lipid peroxidation, and lipid profile were evaluated in the three groups. The BN5 group showed an improvement in all bone parameters compared with that of the CT group (p  < .0001). The BN5 and BN10 groups showed reduced plasma lipid peroxidation compared with that of the CT group (p = .0009), whereas the BN10 group presented lower BAT lipid peroxidation than that of the other groups (p = .01). High-density lipoprotein-cholesterol (HDL-c) levels were higher in the BN5 group than in the CT group (p = .01). Conclusively, the use of BNs in a controlled manner promoted improvement in bone parameters, HDL-c levels, and lipid peroxidation in healthy rats. PRACTICAL APPLICATIONS: Nuts has been included in the diet because of their versatility, acceptance, and easy access. Among them, Brazil nut (BN) is considered one of the major known food sources of selenium as well as a source of fibers, unsaturated fatty acids, and phenolic compounds. Studies have shown that BN supplementation is effective in reducing oxidative stress, inflammation, lipid peroxidation, and selenium deficiency when used as a non-pharmacological strategy in experimental models of chronic diseases and in clinical trials. The present study showed that controlled administration of BN improved bone parameters, high-density lipoprotein-cholesterol levels, and lipid peroxidation in healthy rats. Therefore, BN is a promising non-pharmacological agent for the prevention of the onset of chronic non-communicable diseases.

Amino acid restriction alters survival mechanisms in pancreatic beta cells: possible role of the PI3K/Akt pathway.

BACKGROUND AND AIMS: Malnutrition in the early stages of life may lead to changes in the glycemic metabolism during adulthood, such as pancreatic beta cells dysfunction and failure. Therefore, this study aimed to evaluate the effects of an in vitro amino acid restriction model on the function and viability of pancreatic beta cells. METHODS: Insulin-producing cells (INS-1E) were maintained in control or amino acid restricted culture medium containing 1 × or 0.25 × of amino acids, respectively, for 48 h. RESULTS: Amino acid restricted group showed lower insulin secretion and insulin gene expression, reduced mitochondrial oxygen consumption rate and reactive oxygen species production. Besides, amino acid restricted group also showed higher levels of endoplasmic reticulum stress and apoptosis markers and enhanced Akt phosphorylation. However, even with higher levels of apoptosis markers, amino acid restricted group did not show higher levels of cell death unless the PI3K/Akt pathway was inhibited. CONCLUSION: Amino acid restricted beta cell viability seems to be dependent on the PI3K/Akt pathway.

Amino acid restriction increases ß-cell death under challenging conditions.

Malnutrition programs metabolism, favor dysfunction of ß cells. We aimed to establish an in vitro protocol of malnutrition, assessing the effect of amino acid restriction upon the ß cells. Insulin-producing cells INS-1E and pancreatic islets were maintained in RPMI 1640 medium containing 1× (Ctl) or 0.25× (AaR) of amino acids. We evaluated several markers of ß-cell function and viability. AaR Insulin secretion was reduced, whereas cell viability was unaltered. Calcium oscillations in response to glucose increased in AaR. AaR showed lower Ins1 RNAm, snap 25, and PKC (protein kinase C) protein content, whereas phospho-eIF2α was increased. AaR cells exposed to nutrient or chemical challenges displayed higher apoptosis rates. We showed that amino acid restriction programmed ß cell and induced functional changes. This model might be useful for the study of molecular mechanisms involved with ß-cell programming helping to establish novel therapeutic targets to prevent harmful outcomes of malnutrition.

Maternal soybean diet during lactation alters breast milk composition and programs the lipid profile in adult male rat offspring.

PURPOSE: To evaluate the effects of maternal dietary soybean during lactation on the milk composition, body composition, lipid profile and glucose homeostasis of dams and offspring at weaning (21 days) and adulthood (150 days). METHODS: Lactating rats were divided into: casein control (C): casein diet; soy (S): soybean diet; soy oil control (SOC): casein diet, but with fat content similar to the S group. RESULTS: At 21 days, S mothers showed lower estradiol, total cholesterol (TC), low-density lipoprotein cholesterol (LDL) and triglycerides (TG) in serum; and lower TC and TG in milk. The S offspring had lower body weight, body fat mass, TC, LDL, hyperleptinemia and hypertriglyceridemia. At 150 days, S offspring presented higher total mineral content and lower TC (v. SOC) and LDL (v. C and SOC), and hyperinsulinemia with lower glycemia v. SOC group, which had lower insulinemia with higher glycemia, TC and LDL. CONCLUSIONS: Maternal intake of soybeans in lactation changes the lipid content of breast milk and programmed offspring for phenotype of the lower metabolic risk, with lower serum TC and LDL, and seems to protect the progeny of alterations in glucose metabolism despite the higher lipid content. The difference in fat content of breast milk and the higher isoflavones content of soy diet are possible imprinting factors that could program the offspring.

Dietary calcium supplementation in adult rats reverts brown adipose tissue dysfunction programmed by postnatal early overfeeding.

Brown adipose tissue (BAT) dysfunction is associated with obesity and its comorbidities, such as hypertension, and the improvement of BAT function seems important for obesity management. Here we investigated the effects of dietary calcium supplementation on BAT autonomic nerve activity, sympathoadrenal function and cardiovascular parameters in adult obese rats that were raised in small litters (SL group). Three days after birth, SL litters were adjusted to three pups to induce early overfeeding. The control group remained with 10 pups/litter until weaning (NL group). At PN120, the SL group was randomly divided into the following: rats fed with standard chow (SL) and rats fed with dietary calcium carbonate supplementation (SL-Ca, 10g/kg chow). Animals were killed either at PN120 or PN180. At both ages, SL rats had higher BAT autonomic nervous system activity, mass and adipocyte area, as well as increased heart rate and blood pressure (systolic and diastolic); 2 months of calcium supplementation normalized these parameters. At PN180 only, UCP1 and TRß1 in BAT were decreased in SL rats. These changes were also prevented by calcium treatment. Also at PN180, the SL group presented higher tyrosine hydroxylase and adrenal catecholamine contents, as well as lower hypothalamic POMC and MC4R contents. Calcium supplementation did not revert these alterations. Thus, we demonstrated that dietary calcium supplementation was able to improve cardiovascular parameters and BAT thermogenesis capacity in adult animals that were early overfed during lactation.

Maternal flaxseed oil intake during lactation changes body fat, inflammatory markers and glucose homeostasis in the adult progeny: role of gender dimorphism.

We evaluated maternal flaxseed oil intake during lactation on body composition, lipid profile, glucose homeostasis and adipose tissue inflammation in male and female progeny at adulthood. Lactating rats were divided into the following: control 7% soybean oil (C), hyper 19% soybean oil (HS) and hyper 17% flaxseed oil+2% soybean oil (HF). Weaned pups received a standard diet. Offspring were killed in PN180. Male HF presented higher visceral adipose tissue (VAT) and triacylglycerol, and female HF showed insulin resistance. Both male and female HF had hyperleptinemia, and only male HF had hyperprolactinemia. In VAT, male HF presented lower PPAR-γ expressions and higher TNF-α, IL-6, IL-1ß and IL-10 expressions; in subcutaneous adipose tissue (SAT), they presented lower PPAR-γ and TNF-α expressions. Female HF presented higher leptin, as well as lower adiponectin, TNF-α, IL-6 and IL-1ß expressions in VAT and lower TNF-α in SAT. Flaxseed oil during lactation leads to gender-specific effects with more adiposity and dyslipidemia in male and insulin resistance in female. Higher prolactin and inflammatory cytokines in male could play a role in these gender differences. We suggest that the use of flaxseed oil during lactation increases metabolic syndrome risk in the adult progeny.

Maternal flaxseed diet during lactation changes adrenal function in adult male rat offspring.

Flaxseed (Linum usitatissimum L.) has been a focus of interest in the field of functional foods because of its potential health benefits. However, we hypothesised that maternal flaxseed intake during lactation could induce several metabolic dysfunctions in adult offspring. In the present study, we aimed to characterise the adrenal function of adult offspring whose dams were supplemented with whole flaxseed during lactation. At birth, lactating Wistar rats were divided into two groups: rats from dams fed the flaxseed diet (FLAX) with 25% of flaxseed and controls dams. Pups received standard diet after weaning and male offspring were killed at age 180 days old to collect blood and tissues. We evaluated body weight and food intake during development, corticosteronaemia, adrenal catecholamine content, hepatic cholesterol, TAG and glycogen contents, and the protein expression of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), 11-ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) and adrenaline ß2 receptor at postnatal day 180 (PN180). After weaning, pups from the FLAX group had a higher body weight (+10 %) and food intake (+10%). At PN180, the FLAX offspring exhibited higher serum corticosterone (+48%) and lower adrenal catecholamine ( - 23%) contents, lower glycogen ( - 30%), higher cholesterol (4-fold increase) and TAG (3-fold-increase) contents in the liver, and higher 11ß-HSD1 (+62%) protein expression. Although the protein expression of hypothalamic CRH was unaffected, the FLAX offspring had lower protein expression of pituitary ACTH ( - 34%). Therefore, induction of hypercorticosteronaemia by dietary flaxseed during lactation may be due to an increased hepatic activation of 11ß-HSD1 and suppression of ACTH. The changes in the liver fat content of the FLAX group are suggestive of steatosis, in which hypercorticosteronaemia may play an important role. Thus, it is recommended that lactating women restrict the intake of flaxseed during lactation.

Flaxseed oil during lactation changes milk and body composition in male and female suckling pups rats.

We have reported several changes in neonate or adult offspring after the maternal use of whole flaxseed or its components. However, it is unknown the use of higher oil intake in the neonatal period. Here we evaluated the effects of high maternal intake of flaxseed oil during lactation upon milk and body composition in male and female offspring. Lactating rats were divided into: (1) control (C, n=10), 7% soybean oil; (2) hyper 19% soybean oil (HS, n=10); and (3) hyper 17% flaxseed oil+2% soybean oil (HF, n=10). Dams and offspring were killed at weaning. HS and HF dams, male and female offspring presented lower body weight during lactation. HF mothers presented lower body and visceral fat masses. HF male offspring presented lower body and subcutaneous fat masses. HS and HF milk presented lower triglycerides (TG) and cholesterol. HF male and female offspring showed lower triglyceridemia and insulinemia, but no changes in glycemia and leptinemia. The higher intake of flaxseed oil during lactation reduced the body weight of mothers and offspring, decreases milk lipids and apparently increases insulin sensitivity in this critical period of life. Those changes may explain the previously reported programming effect of maternal flaxseed intake during lactation.

Adipocyte morphology and leptin signaling in rat offspring from mothers supplemented with flaxseed during lactation.

OBJECTIVE: We have recently shown that maternal flaxseed supplementation during lactation induces insulin resistance in adult offspring. Here, we studied the effects of maternal dietary flaxseed during lactation on adipocyte morphology and leptin signaling in the hypothalamic-pituitary-thyroid axis as well as on behavioral traits in the adult progeny. METHODS: Lactating rats were fed a control (C) diet or a diet with 25% flaxseed (F). After weaning, pups received a standard diet until postnatal day (PN) 180. Male offspring were killed at PN21 and 180. Data were considered significant at P < 0.05. RESULTS: Weaned F rats presented a lower total and subcutaneous fat mass and higher subcutaneous adipocyte area (+48%), but at adulthood they presented higher subcutaneous and visceral adipocyte areas (+40% and 1.9-fold increase, respectively), with no change in body fat mass. At PN21, F pups had hyperleptinemia (+69%), lower T(3) (-33%), higher TSH (2.1-fold increase), higher pituitary leptin receptor (Ob-R, +11%), signal transducer and activator of transcription 3 (STAT3, +21%), and phosphorylated-STAT3 (p-STAT3, +77%) protein content. Adult F offspring only showed lower T(4) (-28%) and higher thyroid Ob-R (+52%) expression. Maternal flaxseed intake during lactation did not result in behavioral changes in the adult offspring. CONCLUSIONS: Maternal flaxseed supplementation decreases offspring adiposity and increases pituitary leptin signaling at weaning, but it induces hypertrophic adipocytes and higher thyroid leptin receptor in adulthood. The present data suggest that extensive use of flaxseed during lactation is undesirable.

Efeitos da dieta rica em linhaça na lactação sobre a composição corporal e função tireóidea da prole na idade adulta / Effects of maternal flaxseed diet during lactation on body composition and thyroid function in adult animals

A Linhaça (Linum Usitatissimum) apresenta diversas substâncias com alegados efeitos benéficos que favorecem a diminuição da adiposidade, glicemia e melhoram o perfil lipidêmico e o sistema cardiovascular. Neste trabalho, investigamos na prole 21 e 180 dias de vida o efeito do consumo materno da semente de linhaça durante a lactação sobre os parâmetros associados a composição corporal, a homeostase glicêmica, lipídica e protéica, a leptinemia, adiponectinemia e insulinemia, a função tireoideana e a via de sinalização da leptina no eixo hipotálamo-hipófise-tireóide. As ratas lactantes foram separadas em dois grupos: controle (C) - recebendo ração a base de caseína (20%) e linhaça (L) - recebendo ração adicionada de 25% da semente de linhaça, contendo 18,9% de proteína (sendo 13,9% de caseína e 5% de linhaça) durante a lactação. O sacrifício das proles ocorreu aos 21 e 180 dias de idade, para determinação de: glicemia, albuminemia, proteínas totais, hematócrito, hemoglobina, colesterol total e triglicerídeos, insulina, leptina, adiponectina, TSH, T4 livre e T3 total. Os animais foram completamente eviscerados para obtenção da carcaça e análise da composição corporal. O consumo alimentar e a massa corporal (MC) foram aferidos diariamente durante a lactação e de 4 em 4 dias após a lactação até a idade adulta. As ratas lactantes do grupo L não apresentaram diferença na massa corporal e consumo alimentar. Durante a lactação a prole L apresentou maior ganho de peso corporal e após ao desmame observamos um aumento transitório de massa corporal até a idade adulta. Aos 21 dias, observamos na prole do grupo L menor gordura total e subcutanea, colesterol total, triblicerideo, albumina, insulina, T3 total e atividade de D1 no fígado; e aumento da área dos adipocitos no tecido subcutaneo, leptina, TSH e expressão de Ob-R, STAT3 e p-STAT3 na hipofise (p<0,05). Aos 180 dias, o grupo L apresentou menor glicemia, adiponectina, T4 livre, atividade de D1 e D2 na tireóide...

Flaxseed (Linum usitatissimum) presents high number of substances with alleged beneficial effects that decrease the adiposity, glocuse levels and improved lipid profile and cardiovascular system. In this study, we investigated in the offspring at 21 and 180 days old the effect of maternal consumption of flaxseed during lactation on the parameters associated with body composition, glucose homeostasis, lipid and protein, leptinemia, adiponectinemia and insulinemia, thyroid function, and leptin signaling pathway in the hypothalamus-pituitary-thyroid axis in the offspring at 21 and 180 days old. Lactating rats were divided into: (1) Controls (C), diet containing 20% casein; (2) FLaxseed (F), diet with additional 25% of flaxseed, containing 18.9% protein (13.9% from casein and 5% from flaxseed). The offspring were sacrificed at 21 and 180 days of age to determinate: glycemia, albumin, leptin, adiponectin, TSH, free T4 and total T3. The animals were completely eviscerated to obtain the carcass by body composition analysis. The maternal food intake and body mass were measured daily during the lactation, and after weaning were monitored once every 4 days until they were 180 days old. The dams of F group presented no changes in body mass and food intake. During the lactation the F offspring showed higher body mass and after weaning they presented a higher transitory body mass until 180 days old. At 21 days old, F group showed lower total and subcutaneous fat mass, total cholesterol, triacylglycerol, albumin, insulin, total T3 and D1 liver activity; and higher subcutaneous adipocytes area, leptin, TSH and Ob-R, STAT3 and p-STAT expression in pituitary (p<0,05). At 180 days old, F group presented lower glycemia, adiponectin, free T4 and D1 and D2 activity in thyroid; and higher visceral and subcutaneous adipocytes area, insuli, Ob-R expression in thyroid and D2 activity in brown adipose tissue (p<0,05). In conclusion, maternal flaxseed diet during lactation...

Flaxseed supplementation of rats during lactation changes the adiposity and glucose homeostasis of their offspring.

AIMS: The aim of this paper was to evaluate the effects of maternal dietary flaxseed during lactation on endocrine and metabolic factors in the adult offspring. MAIN METHODS: Lactating rats were divided into: (1) Controls (C), diet containing 20% casein; (2) Flaxseed (F), diet with additional 25% of flaxseed, containing 18.9% protein (13.9% from casein and 5% from flaxseed). The treatment started at birth, day 0 (d0) of lactation, and ended at weaning (d21). After weaning, all pups received a standard laboratory diet until 180 days old. Only male offspring were studied and were sacrificed at 21 or 180 days of age. Body composition was evaluated by carcass analysis. KEY FINDINGS: Offspring from F mothers had higher body mass since lactation until adulthood. At 21 days old, they presented lower total and subcutaneous fat mass, higher leptinemia, lower total cholesterol, lower triacylglycerol and lower insulinemia (p<0.05). At 180 days, offspring from F mothers had lower glycemia, higher insulinemia and lower adiponectin (p<0.05) concentrations and they did not show any changes in body composition. SIGNIFICANCE: Maternal intake of flaxseed in the diet during lactation produces early insulin sensitivity and hyperleptinemia; these hormonal imprinting factors could program for selective insulin resistance, since the higher insulin serum concentration was not associated with higher adiposity. These findings, associated with lower serum adiponectin concentration in adulthood, could indicate an increased risk for later development of diabetes mellitus.