Protein-caloric-restriction diet during lactation programs lean phenotype and improves the antioxidative system in adult female rat offspring.

Nutritional insults early in life, such as during the suckling phase, are associated with phenotypic alterations and promote adverse permanent effects that impair the capacity to maintain energy balance in adulthood. This study aimed to evaluate the long-term effects of a low-protein (LP) diet during lactation on the metabolism and antioxidant systems of adult female rat offspring. Dams were fed a low-protein diet (4% protein) during the first two weeks of lactation or a normal-protein (NP) diet (20% protein) during the entire lactation period. The female offspring received a standard diet throughout the experiment. At 90 days of age, female LP offspring exhibited decreased body weight, feeding efficiency, and fat pad stores. The adult LP female offspring displayed brown adipose tissue hyperplasia without alterations in glucose homeostasis. The LP diet decreased liver triglyceride content and improved the antioxidant system compared to the NP group. The LP diet during the suckling phase promotes a lean phenotype and improves the hepatocyte antioxidant system in adult female offspring. Thus, the LP diet may play an important role in homeostasis and the prevention of metabolic damage.

Epigenetic programming for obesity and noncommunicable disease: From womb to tomb.

Several epidemiological, clinical and experimental studies in recent decades have shown the relationship between exposure to stressors during development and health outcomes later in life. The characterization of these susceptible phases, such as preconception, gestation, lactation and adolescence, and the understanding of factors that influence the risk of an adult individual for developing obesity, metabolic and cardiovascular diseases, is the focus of the DOHaD (Developmental Origins of Health and Disease) research line. In this sense, advancements in molecular biology techniques have contributed significantly to the understanding of the mechanisms underlying the observed phenotypes, their morphological and physiological alterations, having as a main driving factor the epigenetic modifications and their consequent modulation of gene expression. The present narrative review aimed to characterize the different susceptible phases of development and associated epigenetic modifications, and their implication in the development of non-communicable diseases. Additionally, we provide useful insights into interventions during development to counteract or prevent long-term programming for disease susceptibility.

Puberty as a DOHaD programming window: high-fat diet induces long-term hepatic dysfunction in male rats.

The aim of this study was to evaluate whether high-fat (HF) diet intake during puberty can program obesity as well as generate glucose imbalance and hepatic metabolic dysfunctions in adult life. Male Wistar rats were randomly assigned into two groups: rats fed standard chow (NF) and rats fed a HF from postnatal 30-day-old (PND30) until PND60. Then, both groups were fed a standard chow from PND60 until PND120. Euthanasia and samples collections occurred at PND120. HF animals were overweight (+11%) and had increased adiposity, hyperphagia (+12%), hyperglycaemia (+13%), hyperinsulinemia (+69%), and hypertriglyceridemia (+34%). Plasma glucose levels during intravenous glucose tolerance test (ivGTT) and intraperitoneal insulin tolerance test (ipITT) were also higher in the HF group, whereas Kitt was significantly lower (-34%), suggesting reduced insulin sensitivity. In the same sense, HF animals present pancreatic islets hypertrophy and high ß-cell mass. HF animals also had a significant increase in blood glucose levels during pyruvate tolerance test, indicating increased gluconeogenesis. Hepatic morphology analyses showed an increase in lipid inclusion in the HF group. Moreover, PEPCK and FAS protein expression were higher in the livers of the HF animals (+79% and + 37%, respectively). In conclusion, HF during puberty causes obese phenotype leading to glucose dyshomeostasis and nonalcoholic fatty liver disease, which can be related to the overexpression of proteins PEPCK and FAS.

Protein restriction during peripubertal period impairs endothelial aortic function in adult male Wistar rats.

Protein restriction during early phases of body development, such as intrauterine life can favor the development of vascular disorders. However, it is not known if peripubertal protein restriction can favor vascular dysfunction in adulthood. The present study aimed to evaluated whether a protein restriction diet during peripubertal period favors endothelial dysfunction in adulthood. Male Wistar rats from postnatal day (PND) 30 until 60 received a diet with either 23% protein (CTR group) or with 4% protein (LP group). At PND 120, the thoracic aorta reactivity to phenylephrine, acetylcholine, and sodium nitroprusside was evaluated in the presence or absence of: endothelium, indomethacin, apocynin and tempol. The maximum response (Rmax) and pD2 (-log of the concentration of the drug that causes 50% of the Rmax) were calculated. The lipid peroxidation and catalase activity were also evaluated in the aorta. The data were analyzed by ANOVA (one or two-ways and Tukey's) or independent t-test; the results were expressed as mean ± S.E.M., p < 0.05. The Rmax to phenylephrine in aortic rings with endothelium were increased in LP rats when compared with the Rmax in CTR rats. Apocynin and tempol reduced Rmax to phenylephrine in LP aortic rings but not in CTR. The aortic response to the vasodilators was similar between the groups. Aortic catalase activity was lower and lipid peroxidation was greater in LP compared to CTR rats. Therefore, protein restriction during the peripubertal period causes endothelial dysfunction in adulthood through a mechanism related to oxidative stress.

Gestational exposure to continuous light impairs the development of the female reproductive system in adult Wistar rat offspring.

INTRODUCTION: It has been suggested that maternal exposure to constant light during the gestational period could be considered as a chronic stressor, impairing offspring development by interfering in neuroendocrine and behavior responses. OBJECTIVE: This study aimed to evaluate whether maternal exposure to continuous light during pregnancy affects the adult reproductive system in the female offspring. MATERIALS AND METHODS: Pregnant Wistar rats were allocated into light-dark (LD) group, exposed to light and dark photoperiod during gestation, and the light-light (LL) group, exposed to a photoperiod of constant light during gestation. After birth, pups were maintained under normal light-dark photoperiod until adulthood. At postnatal day 90, blood was collected from the female offspring, to analyze plasma luteinizing hormone (LH) and progesterone levels, and the uterus and ovaries were harvested for morphometric, histological, and oxidative stress evaluations. RESULTS AND DISCUSSION: Female exposure to continuous light during the intrauterine period resulted in the adult reduction of LH and increased progesterone plasma levels, and uterine injuries a higher number of endometrial glands and reduced levels of antioxidant enzymes, such as glutathione reductase and glutathione S-transferase. In these experimental conditions, gestational continuous light exposure disturbs sex hormone balance and reduces the antioxidant enzymatic activity in the uterus of female offspring in adult life.

Resveratrol biotransformation and actions on the liver metabolism of healthy and arthritic rats.

AIMS: to investigate the effects of resveratrol on glycogen catabolism and gluconeogenesis in perfused livers of healthy and arthritic rats. The actions of resveratrol-3-O-glucuronide (R3G) and the biotransformation of resveratrol into R3G was further evaluated in the livers. MAIN METHODS: arthritis was induced with Freund's adjuvant. Resveratrol at concentrations of 10, 25, 50, 100 and 200 µM and 200 µM R3G were introduced in perfused livers. Resveratrol and metabolites were measured in the outflowing perfusate. Respiration of isolated mitochondria and activity of gluconeogenic enzymes were also evaluated in the livers. KEY FINDINGS: resveratrol inhibited glycogen catabolism when infused at concentrations above 50 µM and gluconeogenesis even at 10 µM in both healthy and arthritic rat livers, but more sensitive in these latter. Resveratrol above 100 µM inhibited ADP-stimulated respiration and the activities of NADH- and succinate-oxidases in mitochondria, which were partially responsible for gluconeogenesis inhibition. Pyruvate carboxylase activity was inhibited by 25 µM resveratrol and should inhibit gluconeogenesis already at low concentrations. Resveratrol was significantly metabolized to R3G in healthy rat livers, however, R3G formation was lower in arthritic rat livers. The latter must be in part a consequence of a lower glucose disposal for glucuronidation. When compared to resveratrol, R3G inhibited gluconeogenesis in a lower extension and glycogen catabolism in a higher extension. SIGNIFICANCE: the effects of resveratrol and R3G tended to be transitory and existed only when the resveratrol is present in the organ, however, they should be considered because significant serum concentrations of both are found after oral ingestion of resveratrol.

Fecal Microbiota Transplantation During Lactation Programs the Metabolism of Adult Wistar Rats in a Sex-specific Way.

BACKGROUND: The intestinal microbiota is involved in many physiological processes. However, the effects of microbiota in metabolic programming still unknow. We evaluated whether the transplantation of fecal microbiota during early life can program health or disease during adulthood in a model of lean and obese male and female Wistar rats. METHODS: Parental obesity were induced using a small litter (SL, 3 pups/dam) model. At 90 d old, normal litter (NL, 9 pups/dam) and SL males and females (parents) from different litters were mated: NL male vs. NL female; SL male vs. SL female. After birth, male and female offspring rats were also standardized in normal litters or small litters . From the 10th until 25th d of life, the NL and SL male and female offspring received via gavage of a solution containing the diluted feces of the opposite dam (fecal microbiota, M) or saline solution (S). At 90 d of age, biometric and biochemical parameters were assessed. RESULTS: NLM male rats transplanted with obese microbiota showed increased body weight, and fat pad deposition, hyperinsulinemia, glucose intolerance and dyslipidemia. SLM male rats transplanted with lean microbiota had decreased retroperitoneal and mesenteric fat, triglycerides and VLDL levels and improvement of glucose tolerance. Despite SLM female rats showed higher visceral fat, microbiota transplantation in female rats caused no changes in these parameters compared with control groups. CONCLUSION: Fecal microbiota transplantation during lactation induces long-term effects on the metabolism of male Wistar rats. However, female rats were resistant to metabolic alterations caused by the treatment.

Protein Restriction in the Peri-Pubertal Period Induces Autonomic Dysfunction and Cardiac and Vascular Structural Changes in Adult Rats.

Perturbations to nutrition during critical periods are associated with changes in embryonic, fetal or postnatal developmental patterns that may render the offspring more likely to develop cardiovascular disease in later life. The aim of this study was to evaluate whether autonomic nervous system imbalance underpins in the long-term hypertension induced by dietary protein restriction during peri-pubertal period. Male Wistar rats were assigned to groups fed with a low protein (4% protein, LP) or control diet (20.5% protein; NP) during peri-puberty, from post-natal day (PN) 30 until PN60, and then all were returned to a normal protein diet until evaluation of cardiovascular and autonomic function at PN120. LP rats showed long-term increased mean arterial pressure (p = 0.002) and sympathetic arousal; increased power of the low frequency (LF) band of the arterial pressure spectral (p = 0.080) compared with NP animals. The depressor response to the ganglion blocker hexamethonium was increased in LP compared with control animals (p = 0.006). Pulse interval variability showed an increase in the LF band and LF/HF ratio (p = 0.062 and p = 0.048) in LP animals. The cardiac response to atenolol and/or methylatropine and the baroreflex sensitivity were similar between groups. LP animals showed ventricular hypertrophy (p = 0.044) and increased interstitial fibrosis (p = 0.028) compared with controls. Reduced protein carbonyls (PC) (p = 0.030) and catalase activity (p = 0.001) were observed in hearts from LP animals compared with control. In the brainstem, the levels of PC (p = 0.002) and the activity of superoxide dismutase and catalase (p = 0.044 and p = 0.012) were reduced in LP animals, while the levels of GSH and total glutathione were higher (p = 0.039 and p = 0.038) compared with NP animals. Protein restriction during peri-pubertal period leads to hypertension later in life accompanied by sustained sympathetic arousal, which may be associated with a disorganization of brain and cardiac redox state and structural cardiac alteration.

Decisive role of histopathology of lens capsule in the diagnosis of chronic fungal postoperative endophthalmitis.

We report three cases of refractory chronic endophthalmitis after cataract surgery presenting to a referral center, and with repeated negative cultures. Initial treatment consisted of intravitreal and systemic antibiotics, with partial improvement. After subsequent worsening, pars plana vitrectomy, intraocular lens explantation and en bloc capsulectomy were performed. Histopathological examination revealed multiple filamentous fungal structures, sequestered between anterior/posterior lens capsule in all cases. Chronic postoperative fungal endophthalmitis may manifest with negative cultures possibly associated with sequestration of the microorganism into the capsular bag. Careful histopathological examination of lens capsule in these cases may be essential for a definite diagnosis.

Maternal postnatal early overfeeding induces sex-related cardiac dysfunction and alters sexually hormones levels in young offspring.

Postnatal early overfeeding (PO) is a risk factor for cardiometabolic disorders. However, remains unknown the cardiac effects in the second generation from postnatal overfed dams. Our aim was to investigate the effects of maternal PO on cardiac parameters in second generation (F2) offspring. For this, pregnant Wistar rats (F0) were divided into two groups: normal litter (NL, 9 pups) and small litter (SL, 3 pups). At P70, female offspring (F1) of both groups were mated with non-PO male rats. At P21 male and female F2 offspring (NLO and SLO) were weaned, and at P45 they were euthanized to evaluate the cardiac function and sample collection. Male and female SLO showed increased body weight, food intake and adiposity. Blood estradiol levels were increased in the male SLO and decreased in the female SLO. Blood testosterone levels increased in SLO females, but not change in SLO male rats. Although SLO offspring presented cardiac hypertrophy, only males had ex vivo functional impairments, such as reduction of the intraventricular systolic pressure and dP/dt. Male and female SLO had increased interstitial fibrosis; however, only the male SLO had increased perivascular fibrosis. In addition, only male rats from SLO group had decreased AKT and Type 2 Ang-2 receptor, increased catalase and type alpha estrogenic receptor protein levels. Maternal PO leads to obese phenotype and alters sex-steroid levels in both male and female offspring. Although both sexes showed cardiac hypertrophy, only male offspring showed cardiac dysfunction, which may be related with Ang2 and AKT signaling impairments.

Early postnatal exposure of rat pups to methylglyoxal induces oxidative stress, inflammation and dysmetabolism at adulthood.

This work aimed to investigate the effects of early progeny exposure to methylglyoxal (MG), programming for metabolic dysfunction and diabetes-like complications later in life. At delivery (PN1), the animals were separated into two groups: control group (CO), treated with saline, and MG group, treated with MG (20 mg/kg of BW; i.p.) during the first 2 weeks of the lactation period. In vivo experiments and tissue collection were done at PN90. Early MG exposure decreased body weight, adipose tissue, liver and kidney weight at adulthood. On the other hand, MG group showed increased relative food intake, blood fructosamine, blood insulin and HOMA-IR, which is correlated with insulin resistance. Besides, MG-treated animals presented dyslipidaemia, increased oxidative stress and inflammation. Likewise, MG group showed steatosis and perivascular fibrosis in the liver, pancreatic islet hypertrophy, increased glomerular area and pericapsular fibrosis, but reduced capsular space. This study shows that early postnatal exposure to MG induces oxidative stress, inflammation and fibrosis markers in pancreas, liver and kidney, which are related to metabolic dysfunction features. Thus, nutritional disruptors during lactation period may be an important risk factor for metabolic alterations at adulthood.

Lean in one way, in obesity another: effects of moderate exercise in brown adipose tissue of early overfed male Wistar rats.

BACKGROUND: Early postnatal overfeeding (PO) induces long-term overweight and reduces brown adipose tissue (BAT) thermogenesis. Exercise has been suggested as a possible intervention to increase BAT function. In this study, we investigated chronical effects of moderate-intensity exercise in BAT function in postnatal overfed male Wistar rats METHODS: Litters' delivery was on postnatal-day 0 - PN0. At PN2, litters were adjusted to nine (normal litter - NL) or three pups (small litter - SL) per dam. Animals were weaned on PN21 and in PN30 randomly divided into sedentary (NL-Sed and SL-Sed) or exercised (NL-Exe and SL-Exe), N of 14 litters per group. Exercise protocol started (PN30) with an effort test; training sessions were performed three times weekly at 60% of the VO2max achieved in effort test, until PN80. On PN81, a temperature transponder was implanted beneath the interscapular BAT, whose temperature was assessed in periods of lights-on and -off from PN87 to PN90. Sympathetic nerve activation of BAT was registered at PN90. Animals were euthanized at PN91 and tissues collected RESULTS: PO impaired BAT thermogenesis in lights-on (pPO < 0.0001) and -off (pPO < 0.01). Exercise increased BAT temperature in lights-on (pExe < 0.0001). In NL-Exe, increased BAT activity was associated with higher sympathetic activity (pExe < 0.05), ß3-AR (pExe < 0.001), and UCP1 (pExe < 0.001) content. In SL-Exe, increasing BAT thermogenesis is driven by a combination of tissue morphology remodeling (pExe < 0.0001) with greater effect in increasing UCP1 (pExe < 0.001) and increased ß3-AR (pExe < 0.001) content. CONCLUSION: Moderate exercise chronically increased BAT thermogenesis in both, NL and SL groups. In NL-Exe by increasing Sympathetic activity, and in SL-Exe by a combination of increased ß3-AR and UCP1 content with morphologic remodeling of BAT. Chronically increasing BAT thermogenesis in obese subjects may lead to higher overall energy expenditure, favoring the reduction of obesity and related comorbidities.

Protein restriction during lactation causes transgenerational metabolic dysfunction in adult rat offspring.

Introduction: Protein restriction during lactation can induce metabolic dysfunctions and has a huge impact on the offspring's phenotype later in its life. We tested whether the effects of a maternal low-protein diet (LP) in rats can be transmitted to the F2 generation and increase their vulnerability to dietary insults in adulthood. Methods: Female Wistar rats (F0) were fed either a low-protein diet (LP; 4% protein) during the first 2 weeks of lactation or a normal-protein diet (NP; 23% protein). The female offspring (F1 generation) were maintained on a standard diet throughout the experiment. Once adulthood was reached, female F1 offspring from both groups (i.e., NP-F1 and LP-F1) were bred to proven males, outside the experiment, to produce the F2 generation. Male F2 offspring from both groups (NP-F2 and LP-F2 groups) received a standard diet until 60 days old, at which point they received either a normal fat (NF; 4.5% fat) or a high fat diet (HF; 35% fat) for 30 days. Results: At 90 days old, LPNF-F2 offspring had increased lipogenesis and fasting insulinemia compared to NPNF-F2, without alteration in insulin sensitivity. HF diet caused increased gluconeogenesis and displayed glucose intolerance in LPHF-F2 offspring compared to LPNF-F2 offspring. Additionally, the HF diet led to damage to lipid metabolism (such as steatosis grade 3), higher body weight, fat pad stores, and hepatic lipid content. Discussion: We concluded that an F0 maternal protein restricted diet during lactation can induce a transgenerational effect on glucose and liver metabolism in the F2 generation, making the offspring's liver more vulnerable to nutritional injury later in life.

High-fructose diet during puberty alters the sperm parameters, testosterone concentration, and histopathology of testes and epididymis in adult Wistar rats.

The consumption of fructose has increased in children and adolescents and is partially responsible for the high incidence of metabolic diseases. The lifestyle during postnatal development can result in altered metabolic programming, thereby impairing the reproductive system and fertility during adulthood. Therefore, the aim of this study was to evaluate the effect of a high-fructose diet in the male reproductive system of pubertal and adult rats. Male Wistar rats (30 d old) were assigned to four different groups: Fr30, which received fructose (20%) in water for 30 d and were euthanized at postnatal day (PND) 60; Re-Fr30, which received fructose (20%) for 30 d and were euthanized at PND 120; and two control groups C30 and Re-C30, which received water ad libitum and were euthanized at PND 60 and 120, respectively. Fructose induced an increase in abnormal seminiferous tubules with epithelial vacuoles, degeneration, and immature cells in the lumen. Moreover, Fr30 rats showed altered spermatogenesis and daily sperm production (DSP), as well as increased serum testosterone concentrations. After discontinuing high-fructose consumption, DSP and sperm number decreased significantly. We observed tissue remodeling in the epididymis, with a reduction in stromal and epithelial compartments that might have influenced sperm motility. Therefore, we concluded that fructose intake in peripubertal rats led to changes in the reproductive system observed both during puberty and adulthood.

Early postnatal overnutrition impairs VO2max gains with moderate exercise and increase post-exercise muscle damage in adult male rats.

Exercise counteracts obesity effects, but information on how early-life obesity may affect long-term adaptation to exercise is lacking. This study investigates the impact of early-life postnatal overfeeding (PO) on animals' adaptation to exercise. Only male Wistar rats were used. On postnatal day (PN) 30, rats from control (NL-9 pups) or PO (SL-3 pups) litters were separated into four groups: NL-sedentary (NL-Se), NL-exercised (NL-Ex), SL-sedentary (SL-Se), and SL-exercised (SL-Ex). Exercised groups performed moderate-intensity exercise, running on a treadmill, from PN30 to PN90. Further experiments were carried out between PN90 and PN92. PO promoted obesity in SL versus NL rats (P < 0.05). Exercise reduced body weight (P < 0.001), body fat (P < 0.01), and improved glucose homeostasis in SL-Ex versus SL-Se. SL-Ex presented lower VO2max (P < 0.01) and higher post-exercise LDH (P < 0.05) compared to NL-Ex rats. Although moderate exercise counteracted obesity in SL rats, early-life overnutrition restricts fitness gains in adulthood, indicating that early obesity may impair animals' adaptation to exercise.

Metformin Improves Autonomic Nervous System Imbalance and Metabolic Dysfunction in Monosodium L-Glutamate-Treated Rats.

Metformin is an antidiabetic drug used for the treatment of diabetes and metabolic diseases. Imbalance in the autonomic nervous system (ANS) is associated with metabolic diseases. This study aimed to test whether metformin could improve ANS function in obese rats. Obesity was induced by neonatal treatment with monosodium L-glutamate (MSG). During 21-100 days of age, MSG-rats were treated with metformin 250 mg/kg body weight/day or saline solution. Rats were euthanized to evaluate biometric and biochemical parameters. ANS electrical activity was recorded and analyzed. Metformin normalized the hypervagal response in MSG-rats. Glucose-stimulated insulin secretion in isolated pancreatic islets increased in MSG-rats, while the cholinergic response decreased. Metformin treatment normalized the cholinergic response, which involved mostly the M3 muscarinic acetylcholine receptor (M3 mAChR) in pancreatic beta-cells. Protein expression of M3 mAChRs increased in MSG-obesity rats, while metformin treatment decreased the protein expression by 25%. In conclusion, chronic metformin treatment was effective in normalizing ANS activity and alleviating obesity in MSG-rats.

COVID-19 During Development: A Matter of Concern.

A new infectious disease, COVID-19, has spread around the world. The most common symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are cough and fever, but severe cases can develop acute respiratory distress syndrome. The main receptor for SARS-CoV-2 in human tissue is angiotensin-converting enzyme 2, and the lungs, heart, and kidneys are the most affected organs. Besides the inflammatory process and tissue damage, the presence of a cytokine "storm" has been related to a higher mortality rate. Other infectious viral diseases, such as Zika, chikungunya, and influenza, were associated with complications in pregnant women, such as growth restriction, malformation, preterm birth, low birth weight, miscarriage, and death, although they can also cause developmental disorders in infants and adolescents. Evidence points out that stressors during pregnancy and infancy may lead to the development of obesity, diabetes, and cardiovascular disease. Therefore, we hypothesize that COVID-19 infection during the critical phases of development can program the individual to chronic diseases in adulthood. It is important that COVID-19 patients receive proper monitoring as a way to avoid expensive costs to public health in the future.

Extended light period in the maternal circadian cycle impairs the reproductive system of the rat male offspring.

Alterations in the circadian cycle are known to cause physiological disorders in the hypothalamic-pituitary-adrenal and the hypothalamic-pituitary-gonadal axes in adult individuals. Therefore, the present study aimed to evaluate whether exposure of pregnant rats to constant light can alter the reproductive system development of male offspring. The dams were divided into two groups: a light-dark group (LD), in which pregnant rats were exposed to an LD photoperiod (12 h/12 h) and a light-light (LL) group, in which pregnant rats were exposed to a photoperiod of constant light during the gestation period. After birth, offspring from both groups remained in the normal LD photoperiod (12 h/12 h) until adulthood. One male of each litter was selected and, at adulthood (postnatal day (PND) 90), the trunk blood was collected to measure plasma testosterone levels, testes and epididymis for sperm count, oxidative stress and histopathological analyses, and the spermatozoa from the vas deferens to perform the morphological and motility analyses. Results showed that a photoperiod of constant light caused a decrease in testosterone levels, epididymal weight and sperm count in the epididymis, seminiferous tubule diameter, Sertoli cell number, and normal spermatozoa number. Histopathological damage was also observed in the testes, and stereological alterations, in the LL group. In conclusion, exposure to constant light during the gestational period impairs the reproductive system of male offspring in adulthood.

Early AGEing and metabolic diseases: is perinatal exposure to glycotoxins programming for adult-life metabolic syndrome?

Perinatal early nutritional disorders are critical for the developmental origins of health and disease. Glycotoxins, or advanced glycation end-products, and their precursors such as the methylglyoxal, which are formed endogenously and commonly found in processed foods and infant formulas, may be associated with acute and long-term metabolic disorders. Besides general aspects of glycotoxins, such as their endogenous production, exogenous sources, and their role in the development of metabolic syndrome, we discuss in this review the sources of perinatal exposure to glycotoxins and their involvement in metabolic programming mechanisms. The role of perinatal glycotoxin exposure in the onset of insulin resistance, central nervous system development, cardiovascular diseases, and early aging also are discussed, as are possible interventions that may prevent or reduce such effects.