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Childhood and puberty can affect metabolism, leading to tissue injury and malfunction later in life. The consumption of high-processed foods rich in salt and sugar is increasing in middle- and high-income countries, especially among young people. It is necessary to evaluate the effects of high salt and sugar levels in the youth on most injured organs during metabolic challenges. We aimed to investigate whether high salt/sucrose intake affects whole-body development and leads to end-organ injury. Weaned Male Wistar rats were divided into two groups: a control group fed a standard diet (CO) and tap water, and an experimental group (SS) fed a standard diet and a beverage containing 1.8% NaCl and 20% sucrose instead of tap water. The animals were treated for 60 days, starting after weaning at 21 days of age, after which the animals were subjected to glucose and insulin tolerance tests, urine collection, and heart rate monitoring, and euthanized for sample collection at 81 days of age. SS showed reduced body weight gain and increased food intake of sodium/sucrose solution. Interestingly, high salt/sucrose intake led to increased body adiposity, liver lipid inclusion, heart rate, and renal dysfunction. SS exhibits increased levels of peroxisome proliferator-activated receptor alpha to counterbalance the hypertrophy of brown adipose tissue. Our findings reveal that the SS rat model exhibits non-obvious obesity with end-organ damage and preserved brown adipose tissue function. This model closely parallels human conditions with normal BMI but elevated visceral adiposity, providing a relevant tool for studying atypical metabolic disorders.

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.