Effects of free fatty acids and acipimox, a lipolysis inhibitor, on the somatotroph responsiveness to GHRH in anorexia nervosa.
OBJECTIVE
Anorexia nervosa is characterized by low IGF-1 and high GH and free fatty acid (FFA) levels. As FFA exerts an inhibitory feedback action on GH secretion in physiological conditions, we hypothesized that somatotroph cells could be less sensitive to the negative feedback action of FFA in anorexia nervosa.


METHODS
Fifteen patients with anorexia nervosa (AN, age: mean +/- SEM: 20.8 +/- 1.2 years, BMI: 15.9 +/- 0.3 kg/m2) and 12 normal female controls (NW, age 27.2 +/- 2.1 years, BMI 21.2 +/- 2.2 kg/m2).


METHODS
We studied the effects of lipid-heparin emulsion (Li-He, Intralipid 10% 250 ml + heparin 2500 U iv from -60 to + 90 minutes in seven AN and six NW) or acipimox (ACI, 250 mg p.o. at -60 minutes in eight AN and six NW), a lipolysis inhibitor, on the GH response to GHRH (1 microg/kg iv as a bolus at 0 minutes).


RESULTS
Basal IGF-1 levels were lower (P < 0.05) while GH levels were higher (P < 0.05) in AN than in NW. On the other hand, basal FFA levels in the two groups were not significantly different. In both groups Li-He increased FFA levels (P < 0.05), which became higher (P < 0. 02) in AN than in NW. Li-He infusion inhibited (P < 0.05) basal GH levels in AN to levels overlapping those in NW. The GH response to GHRH in the whole AN group was higher than in NW (P < 0.03). Li-He inhibited the somatotroph responsiveness to GHRH in AN (P < 0.03) as well as in NW (P < 0.03) and during Li-He the GH response to GHRH in AN became similar to that in NW. Whilst ACI pretreatment enhanced the GH response to GHRH in AN (P < 0.02), it did not significantly increase that in NW. Interestingly, after ACI administration, FFA levels were inhibited in both groups (P < 0.05) persisting higher in AN than in NW (P < 0.05).


CONCLUSIONS
Though GH hypersecretion in anorexia nervosa occurs in presence of enhanced lipolysis, our present findings indicate that the sensitivity of somatotroph cells to the inhibitory feedback action of free fatty acid is preserved.
Gianotti
L
L
Department of Internal Medicine, University of Turin, Italy.
Fassino
S
S
Daga
G A
GA
Lanfranco
F
F
De Bacco
C
C
Ramunni
J
J
Arvat
E
E
MacCario
M
M
Ghigo
E
E
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D000856:Anorexia Nervosa / Q000097:blood / Q000188:drug therapy*; D016022:Case-Control Studies; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005246:Feedback; D005260:Female; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008055:Lipids / Q000627:therapeutic use*; D011719:Pyrazines / Q000627:therapeutic use*; D018709:Statistics, Nonparametric
D005230:Fatty Acids, Nonesterified; D000960:Hypolipidemic Agents; D008055:Lipids; D011719:Pyrazines; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; C027696:acipimox