Acute pharmacologic blockade of lipolysis normalizes nocturnal growth hormone levels and pulsatility in obese subjects.
Obesity is associated with blunted growth hormone (GH) levels and pulsatility and elevated plasma free fatty acids (FFA) levels. To evaluate whether the two phenomena are correlated, in the present study we investigated the effects of an acute pharmacologic blockade of lipolysis on nocturnal GH levels and pulsatility in 10 obese and 10 control subjects. At 9 PM on two different nights with a 1-night interval in between, all subjects received either a single oral tablet of placebo or acipimox slow release (ACX-SR, 500 mg) in randomized order. Blood samples were drawn from 10 PM to 6 AM for evaluation of FFA, glycerol, GH, immunoreactive insulin (IRI), glucose, and insulin-like growth factor-I (IGF-I) levels. After placebo, FFA and glycerol levels were higher (P < .02) and GH levels, areas, peak amplitude, and peak increment (assessed by the Cluster algorithm) were lower in obese than in control subjects (P < .01). After ACX-SR, FFA and glycerol levels were reduced in both groups (P < .02 v placebo), and in obese subjects they became similar to those observed in control subjects after placebo. ACX-SR had no effect on GH levels and pulsatility in control subjects. GH levels, areas, peak, amplitude, peak increment, and interpeak valley levels were all increased after ACX-SR in obese subjects (P < .05 or less v placebo) and became similar to those observed in normal subjects after placebo, but no correlation was found between the reduction in FFA levels and the increase in GH levels and pulsatility.(ABSTRACT TRUNCATED AT 250 WORDS)
Andreotti
A C
AC
Istituto Scientifico San Raffaele, Milano, Italy.
Lanzi
R
R
Manzoni
M F
MF
Caumo
A
A
Moreschi
A
A
Pontiroli
A E
AE
D000284:Administration, Oral; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D002940:Circadian Rhythm; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005990:Glycerol / Q000097:blood; D013006:Growth Hormone / Q000097:blood*; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism*; D011673:Pulsatile Flow; D011719:Pyrazines / Q000494:pharmacology* / Q000627:therapeutic use
D001786:Blood Glucose; D003692:Delayed-Action Preparations; D005230:Fatty Acids, Nonesterified; D000960:Hypolipidemic Agents; D007328:Insulin; D011719:Pyrazines; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; C027696:acipimox; D005990:Glycerol