Milk-derived extracellular vesicles mitigate NF-κB pathway and NLRP3 inflammasome formation in Long Evans neonates.

Abstract

Exposure to a maternal high fat diet (HFD) during perinatal (prenatal and postnatal combined) life increases offsprings risk of developing metabolic diseases (obesity, type II diabetes and hypertension), impairs immunity, behaviour, and neurodevelopment. Exclusive breast/chest milk feeding is a potential solution to reduce the negative developmental effects of HFD, mainly chronic systemic pro-inflammation. This study focuses on analyzing anti-inflammatory effects of a group of biological nanovesicles found in human milk, entitled milk-derived extracellular vesicles (MEVs). Specifically, we characterized the modulation of the nuclear factor {kappa}B (NF-{kappa}B) signaling pathway and NLR family pyrin domain containing 3 (NLRP3) inflammasome formation by MEVs in male and female neonatal rats with perinatal HFD exposure in the liver and hypothalamus. Female Long Evans dams were placed on a HFD or a control diet (CHD), with matching sucrose levels, 4 weeks before breeding and remained on the diets through gestation and lactation. HFD and CHD offspring received human MEVs through oral gavage twice a day from postnatal day (PND) 4 to 11. Transcript and protein abundance of candidate targets in the NF-{kappa}B signaling pathway and NLRP3 inflammasome were measured by quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western immunoblotting, respectively. Our results indicate that MEV treatment attenuates the activation of NF-{kappa}B pathway and NLRP3 inflammasome formation at critical checkpoints, in males and females with perinatal HFD exposure in liver and the hypothalamus. Taken together, our data suggests that MEVs may elicit anti-inflammatory benefits postnatally that mitigates gestational HFD exposure.