Maternal protein restriction during lactation programs peripheral insulin sensitivity and reduces UCP1 abundance in interscapular brown adipose tissue of adult male Wistar rats

Abstract

Abstract Maternal protein restriction during lactation is associated with stunted growth and hyperphagia in adult offspring, yet its long-term effects on mitochondrial uncoupling-related proteins in interscapular brown adipose tissue (iBAT) remain unknown. This study investigated how postnatal protein undernutrition affects thermogenic regulators and metabolic programming in adult males. Dams received either a low-protein (LP; 4% protein) or normal-protein (NP; 20.5% protein) diet during the first two weeks of lactation. Thereafter, the NP diet was provided to LP dams until weaning and to all offspring from weaning to PND 90. Male offspring were euthanized at postnatal day 90 for somatic, biochemical, hormonal, and iBAT UCP1 and β3-AR protein analyses. Compared with NP controls, LP offspring exhibited reduced body mass, length, and visceral adiposity, despite increased food consumption (all p < 0.0001). They also showed reduced glycemia, insulin, HOMA-β, TyG index, albumin, and HDL-c (all p < 0.05), together with increased peripheral insulin sensitivity assessed by ipITT (p < 0.05). Conversely, LP offspring exhibited increased AST activity and AST/ALT ratio (both p < 0.05) and higher hepatic cholesterol content (p < 0.01). In iBAT, UCP1 protein content was reduced (p < 0.05), whereas β3-AR remained unchanged (p > 0.05). These findings indicate that maternal protein undernutrition during lactation programmed a persistent metabolic phenotype characterized by hyperphagia, reduced somatic growth and visceral adiposity, increased peripheral insulin sensitivity, and lower iBAT UCP1 protein abundance. Collectively, these results suggest long-term alterations in energy partitioning and the iBAT molecular phenotype, although functional thermogenesis was not assessed.