The ghrelin-ghrelin receptor system is one of the most important mechanisms regulating food intake, energy balance and metabolism. Despite the growing interest on nutritional programming of eating disorders, post-natal development of the ghrelin system is currently poorly explored. Moreover, to be fully active, ghrelin must be acylated with medium-chain fatty acids (MCFA) via gastric enzymes (ghrelin-O-acetyl transferase (GOAT), convertase 1/3 (PCSK1/3)). Several reports described dietary modulation of this ghrelin acylation. Therefore, our study aimed at describing early post-natal development of the ghrelin system in mini-pigs as a model of human neonates and the impact of formula-feeding with either a standard or a MCFA-enriched formula on this development.

36 sow-fed piglets were sacrificed 1h after suckling at post-natal day (PND) 0, 2, 5 and 10. In parallel, 18 piglets were fed from birth to PND10 either a standard infant formula (STD-IF) or a dairy lipid -enriched formula to increase MCFA concentration (DL-IF, MCFA 4.7% of total fatty acid vs. 0.1% in STD-IF) and sacrificed 1h after their last meal.

Levels of pre-proghrelin (GHRL) and GOAT mRNA in the antrum did not vary with age (P=0.79), while that of PCSK1/3 dropped by 50% between PND0 and 2 and slightly re-increased thereafter (P<0.0001). Plasma total ghrelin transiently peaked at PND2 and 5 (P=0.007), with no variation of acylated ghrelin fraction concentration (P=0.11). Formula feeding with STD-IF did not modify antrum GHRL and PCSK1/3 mRNA levels (P>0.05) but increased GOAT mRNA (+60%, P=0.05). Total and acylated ghrelin plasma concentration were not affected by STD-IF feeding (P>0.05). DL-IF feeding increased antrum MCFA concentration by 354% (P=0.009) compared to suckling animals but had not impact on GHRL and PCSK1/3 antral mRNA levels (P>0.05) nor on plasma total or acylated ghrelin levels (P>0.05). GOAT mRNA level in MCFA-IF-fed piglets remained significantly greater than in suckling animals (+55%, P=0.03). Plasma acylated/total ghrelin ratio and GOAT mRNA level correlated positively with MCFA concentration in gastric content (r=0.565, P=0.004 and r=0.505, P=0.01, respectively) while GHRL and PCSK1/3 mRNA levels correlated positively with MCFA concentration in gastric tissue (r=0.567, P=0.004 and r=0.459, P=0.02, respectively).

The ghrelin maturation enzyme PCSK1/3 gene expression exhibited transient post-natal modifications in parallel with transient variations in circulating plasma ghrelin level in suckling piglets. Formula feeding slightly impacted GOAT mRNA level with no significant change in circulating ghrelin levels, irrespective of the type of formula tested.