Maternal low protein diet leads to dysregulation of placental iNKT cells and M1/M2 macrophage ratio, body weight loss in male, neonate Sprague‐Dawley rats and increased UCP‐1 mediated thermogenesis

Abstract

Placental immune cells provide cytokines and growth factors that are necessary for placenta development and function. Invariant natural killer T (iNKT) cells are innate cells specific for glycolipid antigens presented by the CD1d molecule and secrete Th1 cytokines in the placenta, suggesting an immunoregulatory role. Self‐lipid antigens at the maternal‐fetal interface may activate iNKT cells, leading to placental inflammation and dysfunction, which can increase brown adipose tissue (BAT) thermogenesis and reduce fetal growth. Maternal low protein (LP) diets reduce offspring birth weight (BW) perhaps via a BAT thermogenesis‐mediated effect. However, whether maternal LP nutrition alters placental immune cell populations and offspring thermogenesis in not yet known. Obese‐prone Sprague‐Dawley dams were fed 8% LP or 20% normal protein (NP) diets for 3 wks prior to breeding and through pregnancy. BW of neonatal LP males was lower than NP males. Vα14 mRNA marker for iNKT cells was 11‐fold higher in LP placenta, while there was also an increase in proinflammatory M1/M2 macrophage mRNA marker ratio. UCP‐1 gene and protein expression and transcription factors PRDM16 and PPARα in BAT were 2‐ to 6‐fold greater in LP than NP neonatal males. FNDC5, an irisin precursor and thermogenesis activator, was 2‐fold greater in neonatal LP BAT than NP males. These results suggest that prenatal protein restriction increases proinflammatory iNKT and M1 macrophages in the placenta, leading to placental dysfunction, increased offspring BAT thermogenesis, and low BW.