Gestational low dietary protein induces intrauterine inflammation and alters the programming of adiposity and insulin sensitivity in the adult offspring.

Malnutrition associated with low dietary protein can induce gestational inflammation and sets a long-lasting metabolic impact on the offspring even after replenishment. The work investigated whether a low-protein diet (LPD) during pregnancy and lactation induces intrauterine inflammation and predisposes offspring to adiposity and insulin resistance in their adult life. Female Golden Syrian hamsters were fed LPD (10.0% energy from protein) or a control diet (CD, 20.0 % energy from protein) from preconception until lactation. All pups were switched to CD after lactation and continued until the end. Maternal LPD increased intrauterine inflammation by enhancing neutrophil infiltration, amniotic hsCRP, oxidative stress, and mRNA expression of NFκβ, IL8, COX2, and TGFβ in the chorioamniotic membrane (P<.05). The prepregnancy body weight, placental, and fetal weights, serum AST and ALT were decreased, while blood platelets, lymphocytes, insulin, and HDL were significantly increased in LPD-fed dams (P<.05). A postnatal switch to an adequate protein could not prevent hyperlipidemia in the 6-months LPD/CD offspring. The lipid profile and liver functions were restored over 10 months of protein feeding but failed to normalize fasting glucose and body fat accumulation compared to CD/CD. LPD/CD showed elevated GLUT4 expression & activated pIRS1 in the skeletal muscle and increased expression of IL6, IL1β, and p65-NFκB proteins in the liver (P<.05). In conclusion, present data suggest that maternal protein restriction may induce intrauterine inflammation and affect liver inflammation in the adult offspring by an influx of fats from adipose that may alter lipid metabolism and reduce insulin sensitivity in skeletal muscle.