Neonatal high-dose riboflavin treatment channels energy expenditure towards sensorimotor and somatic development and reduces rodent growth and weight gain by modulating NRF-1 in the hypothalamus

Abstract

Metabolic adaptations early in life can drive energy expenditure towards brain and physical development, with less emphasis on body mass gain and somatic growth. Dietary or pharmacological manipulations can influence these processes, but to date, the effects provided by riboflavin have not been studied. The study aimed to evaluate the effects of neonatal treatment with different doses of riboflavin on sensorimotor and somatic development in rodents. Based on this, the following experimental groups were formed: Control (C, 0 mg/kg), Riboflavin 1 (R1, 1 mg/kg), Riboflavin 2 (R2, 10 mg/kg) and Riboflavin 3 (R3, 100 mg/kg). Treatment with 100 mg/kg riboflavin anticipated the reflex ontogeny of righting, cliff aversion, negative geotaxis, and free-fall righting. Intervention with 10 and 100 mg/kg of riboflavin anticipated the reflex maturation of vibrissae placement. Eye-opening, upper incisor eruption, and lower incisor eruption reached maturational age more quickly for animals treated with 100 mg/kg, while caudal growth and body weight gain were reduced from the second week of treatment, for groups R2 and R3. Pearson's correlation analysis indicated a positive association between the administration of high doses of riboflavin and murine growth in the first week of treatment. There was, however, a negative association between treatment with a high dose of riboflavin and growth in the second week of administration, coinciding with a reduction in body weight gain in the R3 group. Treatment with 100 mg/kg of riboflavin also reduced energy expenditure parameters in the open field and catwalk. Although high-dose treatment stimulates the physiological plasticity of the CNS and reduces weight gain, hepatic parameters were preserved, highlighting the participation of the liver in the supply of fatty acids for neural maturation. Furthermore, hypothalamic NRF-1 expression was increased in the R3 group inversely to the reduction in weight gain. Our results suggest that high-dose riboflavin stimulates sensorimotor and somatic development and reduces the energy invested in growth, body weight gain, and locomotor activity, possibly involving NRF-1 gene modulation in the hypothalamus.