Hypothalamic Mediated Action of Free Fatty Acid on Growth Hormone Secretion in Sheep
Experimental data suggest that elevated FFA levels play a leading role in the impaired GH secretion in obesity and may therefore contribute to the maintenance of overweight. GH has a direct lipolytic effect on adipose tissue; in turn, FFA elevation markedly reduces GH secretion. This suggests the ex...
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Published in | Endocrinology (Philadelphia) Vol. 139; no. 12; pp. 4811 - 4819 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Endocrine Society
01.12.1998
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Subjects | |
Online Access | Get full text |
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Summary: | Experimental data suggest that elevated FFA levels play a leading role
in the impaired GH secretion in obesity and may therefore contribute to
the maintenance of overweight. GH has a direct lipolytic effect on
adipose tissue; in turn, FFA elevation markedly reduces GH secretion.
This suggests the existence of a classical endocrine feedback loop
between FFA and GH secretion. However, the FFA mechanism of action is
not yet understood. The involvement of somatostatin (SRIH) is
controversial, and in vitro experiments suggest a direct
effect of FFA on the pituitary. In sheep it is possible to collect
hypophysial portal blood and quantify SRIH secretion in hypophysial
portal blood under physiological conscious and unstressed conditions.
In this study we determined the effects of FFA (Intralipid and heparin)
infusion on peripheral GH and portal SRIH levels in intact rams
chronically implanted with perihypophysial cannula and in rams actively
immunized against SRIH to further determine SRIH-mediated FFA effects
on GH axis.
Immediately after initiation of Intralipid infusion, we observed a
marked increase in the FFA concentration (2160 ± 200
vs. 295 ± 28 nmol/ml; P <
0.01) as well as a significant decrease in basal GH secretion (1.8±
0.1 vs. 2.5 ± 0.3 ng/ml; P< 0.05) and a drastic reduction of the GH response to iv GH-releasing
hormone injection (4.8 ± 0.7 ng/ml in FFA group
vs. 35.8 ± 9.7 ng/ml in saline group;
P < 0.01). No change in plasma insulin-like growth
factor I levels was observed. During the first 2 h of infusion,
the GH decrease observed was concomitant with a significant increase in
portal SRIH levels (22.1 ± 3.2 vs. 13 ± 1.6
pg/ml; P < 0.01). In rams actively immunized
against SRIH, the effect of FFA on basal GH secretion was biphasic.
During the first 90 min of infusion, the decrease in GH induced by FFA
was significantly blunted in rams actively immunized against SRIH
(57 ± 9% for immunized rams vs. 23.5 ±
2.5% for control rams). This corresponds to the period of increased
SRIH portal levels. After this first 90-min period, no difference was
seen between control and immunized rams.
Our results show that FFA exert their inhibitory action on the GH axis
at both pituitary and hypothalamic levels, the latter mainly during the
first 90 min, through increased SRIH secretion. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0013-7227 1945-7170 |
DOI: | 10.1210/endo.139.12.6356 |