INVESTIGADORES
GIOVAMBATTISTA Andres
artículos
Título:
Food Intake-Induced Leptin SecretionModulates Hypothalamo-Pituitary-Adrenal Axis Response and Hypothalamic Ob-Rb Expression to Insulin Administration
Autor/es:
GIOVAMBATTISTA, A; CHISARI, A; GAILLARD, R; SPINEDI, E
Revista:
NEUROENDOCRINOLOGY
Editorial:
Karger
Referencias:
Lugar: Switzerland; Año: 2000 vol. 72 p. 341 - 349
ISSN:
0028-3835
Resumen:
The mutation of the ob gene is known to induce a phenotype
of obesity accompanied by symptoms including
enhanced production of glucocorticoid. Chronic administration
to ob/ob mice of leptin, the ob gene product,
reverses hypercorticosteronemia. This establishes a
clear relation between adipocyte and hypothalamo-pituitary-
adrenal (HPA) axis functions. In the present study
we investigated the acute modulatory effects of food
intake-stimulated leptin secretion on HPA axis activity
and hypothalamic leptin receptor (Ob-Rb) expression in
24-hour fasting, adult female, BALBlc mice after insulininduced
hypoglycemia. Our results indicate that: (1) food
supply for 45 min to 24-hour fasting mice increased plasma
glucose levels and reversed both hypercorticosteronemia
and hypoleptinemia; (2) the insulin-induced hypoglycemia
produced a marked HPA axis activation in animals
with no access to food but this response was fully
prevented by food intake and the consecutive increase in
plasma leptin levels; (3) the inhibitory effect of leptin on
the HPA axis response to insulin-induced hypoglycemia
was corroborated by i.p. administration of murine leptin,
and (4) fasting-induced hypothalamic Ob-Rb overexpression
is not modulated by insulin itself but by leptin,
since increase in leptin levels by food intake or by
administration of exogenous leptin completely reversed
this Ob-Rb overexpression. These results confirm the
inhibitory effect of leptin on the HPA axis response to
various stress stimuli. They clearly demonstrate that
acute food intake in 24-hour fasting mice: (a) rapidly
reduced fasting-induced hypercorticosteronemia by enhancing
both spontaneous and insulin-elicited endogenous
leptin secretion; (b) fully prevented HPA axis response
to insulin administration, by rapidly increasing
endogenous leptin secretion and probably also by diminishing
the extent and the duration of insulin-induced
hypoglycemia, and (c) abolished hypothalamic Ob-Rb
overexpression induced by fasting itself combined with
insulin treatment. The present data strongly suggests aninhibitory effect of endogenous leptin on insulin-induced
HPA axis response, an interaction relevant to the physiological
adaptation to starvation and caloric excess, and
further supports the pivotal role played by the hypothalamus
in restoring homeostasis in different allostatic
states.