High-dose neonatal riboflavin remodels energy metabolism and brain mitochondrial ultrastructure in rats exposed to maternal high-fat diet.

Changes in maternal nutritional status during conception are associated with fetal metabolic programming. Overexposure to metabolic disruptors can impair fetal growth and development and predispose to chronic diseases later in life. We report that high-dose riboflavin treatment (100 mg/kg) improved energy supply during normal development and reduced metabolic dysfunction resulting from maternal obesity. Male Wistar rats from control or hyperlipidemic mothers were included in the study and treated subcutaneously with riboflavin or vehicle during lactation. Riboflavin treatment reduced weight gain and improved glycemic response, increasing sensitivity during the glucose tolerance test in control rats (p < 0.05). Furthermore, it reduced serum triglyceride and glucose (p < 0.05), and increased the expression of glucose transporters in peripheral tissues (p < 0.0001). Riboflavin reduced adipose tissue accumulation (p < 0.05; p < 0.01) and improved hypothalamic expression of the energy balance-regulating hormones Pomc (p < 0.01) and Npy (p < 0.05) in rats subjected to adverse metabolic programming. It also stimulated the expression of Ppargc1a (PGC-1α) in both the brain (p < 0.01) and peripheral tissues, as well as glucose transporters in the periphery (p < 0.05; p < 0.0001). TEM analysis showed that riboflavin treatment enhanced mitochondrial biogenesis, as evidenced by an increased aspect ratio in high-lipid offspring and greater mitochondrial area in healthy rats (p < 0.05). Our findings demonstrate the effects of high-dose riboflavin on molecular, biochemical, behavioral, and ultrastructural parameters, offering new perspectives for metabolic interventions at critical developmental stages.