INVESTIGADORES
GIOVAMBATTISTA Andres
artículos
Título:
Maternal undernutrition induces neuroendocrine immune dysfunction in male pups at weaning.
Autor/es:
CHISARI, A; GIOVAMBATTISTA A; PERELLO, M; GAILLARD, R; SPINEDI, E
Revista:
NEUROIMMUNOMODULATION.
Editorial:
KARGER
Referencias:
Lugar: Basel; Año: 2001 vol. 9 p. 41 - 48
ISSN:
1021-7401
Resumen:
The present study was designed to assess the effect of maternal
undernutrition, during gestation and lactation, on the neuroendocrine
[hypothalamo-pituitary-adrenal (HPA)]-immune axis response to endotoxin (LPS)
administration. 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 vehicle alone (VEH) or containing LPS (130 microg/kg BW). Circulating levels
of glucose (GLU), ACTH, corticosterone (B), tumor necrosis factor-alpha
(TNFalpha) 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 LPS treatment did not induce hypoglycemia,
in either group; (c) basal plasma ACTH, B and TNFalpha levels were similar in
the two groups, and LPS-induced ACTH, B and TNFalpha secretions, although
severalfold higher than respective VEH values (p < 0.05) in pups from WN
mothers, were fully (ACTH and B) and partially (TNFalpha) abolished in products
from UN mothers; (d) both mean body weights and basal plasma leptin levels were
significantly (p < 0.05) lower in pups from UN than from WN mothers, and LPS
administration did not modify plasma leptin values in products 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 pups, 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 inhibit ACTH-stimulated
glucocorticoid release by AG cells from UN pups. The present results indicate
that undernutrition in mothers, during the very critical periods of gestation
and lactation, induces in their male pups at weaning: (a) reduced circulating
leptin levels and body weight values; (b) metabolic adaptation to normal
carbohydrate metabolism; (c) hyporesponsiveness of the HPA and immune
(TNFalpha) axes during endotoxemia, and (d) leptin resistance at the
adrenocortical level. This study strongly supports that undernutrition of
mothers results in neuroendocrine immune dysfunction of their pups; however,
adrenal resistance to the inhibitory effect of leptin on glucocorticoid output
is developed, probably as an adaptive mechanism to counteract unfavorable
metabolic conditions.