Effects of GH replacement therapy in adults on serum levels of leptin and ghrelin: the role of lipolysis.
OBJECTIVE
The regulation and function of systemic ghrelin levels appear to be associated with food intake and energy balance rather than GH. Since GH, in turn, acutely induces lipolysis and insulin resistance in skeletal muscle, we aimed to study the isolated and combined effects of GH, free fatty acids (FFAs) and insulin sensitivity on circulating ghrelin levels in human subjects.


METHODS
Seven GH-deficient patients (aged 37 +/- 4 years (mean +/- s.e.)) were studied on four occasions in a 2 x 2 factorial design with and without GH substitution and with and without administration of acipimox, which lowers FFA levels by inhibition of the hormone-sensitive lipase, in the basal state and during a hyperinsulinemic euglycemic clamp.


RESULTS
Serum FFA levels decreased with acipimox administration irrespective of GH status. The GH-induced reduction in insulin sensitivity was countered by acipimox. Fasting ghrelin levels decreased insignificantly during GH administration alone, but were reduced by 33% during co-administration of GH and acipimox (Aci) (in ng/l): 860 +/- 120 (-GH - Aci), 711 +/- 130 (-GH + Aci), 806 +/- 130 (+GH - Aci), 574 +/- 129 (+GH + Aci), P < 0.01. The clamp was associated with a further, moderate lowering of ghrelin. GH and acipimox induced a reciprocal 25% increase in serum leptin levels (microg/l): 11.2 +/- 4.4 (-GH - Aci), 11.7 +/- 4.4 (-GH + Aci), 11.5 +/- 4.4 (+GH - Aci), 13.9 +/- 4.2 (+GH + Aci), P = 0.005.


CONCLUSIONS
Our data suggest that antilipolysis via suppression of the hormone-sensitive lipase in combination with GH administration is associated with significant and reciprocal changes in ghrelin and leptin.
Vestergaard
E T
ET
Medical Department M (Endocrinology and Diabetes), Aarhus University Hospital, Dk-8000 Aarhus C, Denmark. etv@dadlnet.dk
Hansen
T K
TK
Nielsen
S
S
Moller
N
N
Christiansen
J S
JS
Jorgensen
J O L
JO
D000328:Adult; D004338:Drug Combinations; D005215:Fasting / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D054439:Ghrelin; D013006:Growth Hormone / Q000627:therapeutic use*; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000172:deficiency / Q000378:metabolism*; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood*; D008066:Lipolysis; D008297:Male; D008875:Middle Aged; D036361:Peptide Hormones / Q000097:blood*; D011719:Pyrazines / Q000627:therapeutic use; D043202:Steroid Metabolism, Inborn Errors / Q000188:drug therapy*; D002787:Sterol Esterase / Q000037:antagonists & inhibitors
D004338:Drug Combinations; D005230:Fatty Acids, Nonesterified; D054439:Ghrelin; D000960:Hypolipidemic Agents; D020738:Leptin; D036361:Peptide Hormones; D011719:Pyrazines; D019382:Human Growth Hormone; D013006:Growth Hormone; D002787:Sterol Esterase; C027696:acipimox