Maternal Western diet alters milk leptin levels and early postnatal leptin handling in rat offspring

: Lactation is a critical developmental window during which maternal conditions influence breast milk composition, thereby affecting infant growth and long-term health. Leptin, a key bioactive component of breast milk involved in metabolic programming, may have its beneficial effects attenuated under maternal obesogenic diets. This study evaluated whether a maternal Western-style diet (WD) is associated with changes in early postnatal absorption of milk-derived leptin and leptin-related miRNAs, and their relationship with gastric content as an indirect indicator of nutrient intake in the offspring. Female rats were fed a control diet (C-Dams) or a WD (WD-Dams) starting one month before gestation and throughout gestation and lactation. Dams and pups were euthanized at lactation/postnatal day 4 (LD4/PND4). WD-Dams displayed higher leptinemia (3.8 ± 1.5 vs. 2.1 ± 0.67 ng/mL, p = 0.026) and milk leptin levels (1.6 ± 0.46 vs. 1.0 ± 0.33 ng/mL, p = 0.012). Despite increased milk leptin supply and stronger gastric leptin signal detected by immunohistochemistry, WD-pups did not show a quantitative increase in gastric leptin content or circulating leptin levels. Notably, they presented a tendency towards greater gastric content (0.24 ± 0.12 vs. 0.12 ± 0.11 g, p = 0.089). No differences were found in leptin-related miRNAs absorption; however, miR-17 levels were higher in WD-milk (increment of 70.7%) and correlated with duodenal levels only in WD-pups. Maternal WD consumption during the perinatal period alters milk leptin levels and early leptin exposure and is associated with slight differences in gastric content in the offspring, suggesting early alterations in regulatory processes.