Maternal undernutrition induces neuroendocrine immune dysfunction in male pups at weaning

The present study was designed to assess the effect of maternal undernutrit ion, during gestation and lactation, on the neuroendocrine [hypothalamo-pit uitary-adrenal (HPA)]-immune axis response to endotoxin (LPS) administratio n. For this purpose, 21-day-old male rats from both well-nourished (WN) and undernourished (UN) mothers were examined 2 h after injection (i.p.) of ve hicle alone (VEH) or containing LPS (130 mug/kg BW). Circulating levels of glucose (GLU), ACTH, corticosterone (B), tumor necrosis factor-alpha (TNF a lpha) and leptin were explored. The results indicate that: (a) mother body weight was significantly (p < 0.05) reduced, as a consequence of UN, at the second and third weeks of pregnancy; (b) no differences in basal glycemia were found in the two groups of pups, and LIPS treatment did not induce hyp oglycemia, in either group; (c) basal plasma ACTH, B and TNFa levels were s imilar in the two groups, and LPS-induced ACTH, B and TNFa secretions, alth ough severalfold higher than respective VEH values (p < 0.05) in pups from WN mothers, were fully (ACTH and B) and partially (TNF alpha) abolished in products from UN mothers; (d) both mean body weights and basal plasma lepti n levels were significantly (p < 0.05) lower in pups from UN than from WN m others, and LPS administration did not modify plasma leptin values in produ cts from both groups. In addition, results of dispersed total adrenal cells incubated in vitro indicate that: (a) both basal and ACTH (22 pM)-induced B secretion were significantly (p < 0.05) lower in cells from UN than WN pu ps, and (b) leptin (100 nM) was able to inhibit partially ACTH-stimulated B output by adrenal gland (AG) cells from WN pups; however, it failed to inh ibit ACTH-stimulated glucocorticoid release by AG cells from UN pups. The p resent results indicate that undernutrition in mothers, during the very cri tical periods of gestation and lactation, induces in their male pups at wea ning: (a) reduced circulating leptin levels and body weight values; (b) met abolic adaptation to normal carbohydrate metabolism; (c) hyporesponsiveness of the HPA and immune (TNFa) axes during endotoxemia, and (d) leptin resis tance at the adrenocortical level. This study strongly supports that undern utrition of mothers results in neuroendocrine immune dysfunction of their p ups; however, adrenal resistance to the inhibitory effect of leptin on gluc ocorticoid output is developed, probably as an adaptive mechanism to counte ract unfavorable metabolic conditions. Copyright (C) 2001 S. Karger AG, Bas el.