Obesogenic environments such as Westernized diets, overnutrition, and exposure to glycation during gestation and lactation can alter peripheral neuroendocrine factors in offspring, predisposing for metabolic diseases in adulthood. Thus, we hypothesized that exposure to obesogenic environments during the perinatal period reprograms offspring energy balance mechanisms. Four rat obesogenic models were studied: maternal diet-induced obesity (DIO); early-life obesity induced by postnatal overfeeding; maternal glycation; and postnatal overfeeding combined with maternal glycation. Metabolic parameters, energy expenditure, and storage pathways in visceral adipose tissue (VAT) and the liver were analyzed. Maternal DIO increased VAT lipogenic [NPY receptor-1 (NPY1R), NPY receptor-2 (NPY2R), and ghrelin receptor], but also lipolytic/catabolic mechanisms [dopamine-1 receptor (D1R) and p-AMP-activated protein kinase (AMPK)] in male offspring, while reducing NPY1R in females. Postnatally overfed male animals only exhibited higher NPY2R levels in VAT, while females also presented NPY1R and NPY2R downregulation. Maternal glycation reduces VAT expandability by decreasing NPY2R in overfed animals. Regarding the liver, D1R was decreased in all obesogenic models, while overfeeding induced fat accumulation in both sexes and glycation the inflammatory infiltration. The VAT response to maternal DIO and overfeeding showed a sexual dysmorphism, and exposure to glycotoxins led to a thin-outside-fat-inside phenotype in overfeeding conditions and impaired energy balance, increasing the metabolic risk in adulthood.

Background: Though maternal diabetes effects are well described in the literature, the effects of maternal diabetes in postnatal phases are often overlooked. Diabetic individuals have higher levels of circulating glycotoxins, and there is a positive correlation between maternal-derived glycotoxins and circulating glycotoxins in their progeny. Previous studies evaluated the metabolic effects of high glycotoxin exposure during lactation in adult animals. However, here we focus on the cardiovascular system of juvenile rats. Methods: For this, we used two experimental models: 1. High Methylglyoxal (MG) environment: pregnant Wistar rats were injected with PBS (VEH group) or Methylglyoxal (MG group; 60 mg/kg/day; orally, postnatal day (PND) 3 to PND14). 2. GLO-1 inhibition: pregnant Wistar rats were injected with dimethyl sulfoxide (VEH group) or a GLO-1 inhibitor (BBGC group; 5 mg/kg/day; subcutaneously, PND1–PND5). The offspring were evaluated at PND45. Results: MG offspring presented cardiac dysfunction and subtly worsened vasomotor responses in the presence of perivascular adipose tissue, without morphological alterations. In addition, an endogenous increase in maternal glycotoxins impacts offspring vasomotricity due to impaired redox status. Conclusions: Our data suggest that early glycotoxin exposure led to cardiac and vascular impairments, which may increase the risk for developing cardiovascular diseases later in life.

Obesity and the intake of high-sugar diets have dramatically increased in recent decades. However, it is still uncertain how sugar intake during the critical development phase affects the long-term health of children. In this context, the Developmental Origins of Health and Disease (DOHaD) concept established a correlation between early life environment and the development of cardiometabolic diseases in adulthood. This review summarizes the current knowledge about the consequences of sugar intake during the critical development phase for the onset of non-communicable diseases (NCDs). We found evidence that increased sugar intake during pregnancy contributes to maternal obesity and many cardiometabolic dysfunctions in the offspring. Furthermore, dietary sugar during the suckling period provokes the obese phenotype in adulthood. Finally, high-sugar diet intake during childhood induces metabolic syndrome and depressive-like behavior.

Ghrelin has effects that range from the maturation of the central nervous system to the regulation of energy balance. The production of ghrelin increases significantly during the first weeks of life. Studies have addressed the metabolic effects of liver-expressed antimicrobial peptide 2 (LEAP2) in inhibiting the effects evoked by ghrelin, mainly in glucose homeostasis, insulin resistance, and lipid metabolism. Despite the known roles of ghrelin in the postnatal development, little is known about the long-term metabolic influences of modulation with the endogenous expressed growth hormone secretagogue receptor (GHSR) inverse agonist LEAP2. This study aimed to evaluate the contribution of GHSR signalling during perinatal phases, to neurodevelopment and energy metabolism in young animals, under inverse antagonism by LEAP2_[1–14]. For this, two experimental models were used: (i) LEAP2_[1–14] injections in female rats during the pregnancy. (ii) Postnatal modulation of GHSR with LEAP2_[1–14] or MK677. Perinatal GHSR modulation by LEAP2_[1–14] impacts glucose homeostasis in a sex and phase-dependent manner, despite no effects on body weight gain or food intake. Interestingly, liver PEPCK expression was remarkably impacted by LEAP2 injections. The observed results suggests that perinatal LEAP2 exposure can modulate liver metabolism and systemic glucose homeostasis. In addition, these results, although not expressive, may just be the beginning of the metabolic imbalance that will occur in adulthood.

Background: Advanced glycation end-products (AGEs) are linked to the development of oxidative stress, insulin resistance, and impaired insulin secretion. Adverse early life conditions, such as exposure to AGEs and their precursors, may lead offspring to the development of metabolic dysfunction in adulthood. Nonetheless, the early impact in offspring metabolism by maternal intake of AGEs precursors during lactation is not known. Objective: Investigate early life metabolism of the offspring whose breastfeeding dams were orally exposed to AGEs precursor. Methods: Breastfeeding Wistar rats were daily treated with the glycation precursor methylglyoxal (MG—60 mg/kg of bodyweight) by gavage or saline 0.9% control (CO) until weaning. In vivo glycemic homeostasis in male offspring was assessed, followed by euthanasia for tissue sample collection for ex vivo assessments. Results: At weaning, MG offspring presented decreased bodyweight (p < 0.05), perigonadal (p < 0.01) and retroperitoneal (p < 0.01) fat. MG offspring presented decreased glucose tolerance (p < 0.05), lower basal insulinemia (p < 0.001), reduced high-glucose static insulin secretion (p < 0.05), and reduced pancreatic islet area (p < 0.05). Accordingly, MG offspring pancreas showed lower GSH and SOD activity (p < 0.05; p < 0.001, respectively) and increased MPO (p < 0.05) activity. Conclusions: The consumption of AGE precursors by breastfeeding dams impaired offspring pancreatic function and glycemic homeostasis early in life.