Oleic acid-enriched diet improves maternal lactation performance and neonatal growth through GPR40 and GPR120 signaling pathways

Oleic acid represents a major monounsaturated component of milk fat, yet its specific roles in lactation remain unclear. This study evaluated the impact of an oleic acid-enriched diet on sow lactation performance, milk composition, and offspring growth, and investigated the underlying regulatory mechanisms. Eighty sows were randomized to either a standard diet or a high-oleic acid diet formulation throughout gestation and lactation. The milk fat content, fatty acid profiles, and weaning body weight of the litter were measured. In parallel, porcine mammary epithelial cells (pMECs) were treated with oleic acid, with or without selective inhibitors of GPR40 and GPR120, to dissect receptor-mediated effects on triglyceride synthesis and fatty acid transporter expression. Dietary enrichment with oleic acid significantly increased milk fat content, shifted the milk fatty acid profile toward higher monounsaturated levels, and resulted in greater weaning body weight in piglets. Enhanced transfer of immunoglobulins, antioxidant enzymes, and inflammatory mediators from sow to neonate further suggested improved neonatal resilience. In pMECs, oleic acid upregulated CD36, FATP4, and FABP3 expression and boosted triglyceride synthesis via activation of both GPR40 and GPR120. Pharmacological blockade revealed that GPR40 inhibition reduced triglyceride accumulation by approximately 37.6%, whereas GPR120 blockade produced a more modest decrease. Together, these findings demonstrate that oleic acid enhances milk fat production and supports offspring growth through GPCR-dependent signaling, with GPR40 playing the dominant role.