Alcohol ingestion decreases both diurnal and nocturnal secretion of leptin in healthy individuals.
OBJECTIVE
Neuropeptide Y (NPY) stimulates appetite and increases food intake. Leptin inhibits NPY. It is not known whether alcohol influences any of these factors, but it has been suggested that alcohol stimulates appetite in man. The primary objective of this investigation was to determine whether ingestion of ethanol inhibits leptin secretion in normal subjects.


METHODS
Fourteen healthy, non-obese subjects of both sexes (7 F/7 M) were included. They were divided into two groups (I and II; 8/6). All were investigated on two occasions. On one occasion alcohol was ingested, and on the other drinking water was given. The experiments took place in random order, one week apart. In group I two experiments (A = alcohol; B = water) were performed during the day. In group II the experiments were carried out during the night (C = alcohol; D = water). Each alcoholic drink contained 0.45 g ethanol/kg. The drinks were given at 08.00, 09.30 and 11.00 hours in experiments A and B, and at 18.00, 20.00 and 22.00 hours in experiments C and D. Venous blood samples were collected before, during and after the drinks over periods of 6 h in group I and 14 h in group II.


METHODS
Serum concentrations of leptin, insulin-like growth factor 1 (IGF-1), IGF binding protein 1 (IGFBP-1), insulin, cortisol, testosterone, ethanol and plasma glucose were determined. RESULTS Group I serum leptin levels declined during the day in both men and women regardless of whether alcohol or water had been administered in the morning. Since leptin levels in general were markedly higher in women than in men, all leptin changes after water/alcohol were transformed to percentage changes to make them comparable between sexes. When the percentage leptin decline over a 6-h period (08.00-24.00 hours) was expressed by a decremental area under curve (AUC08-14), it became evident that alcohol inhibited leptin secretion, inasmuch as the leptin decremental area, obtained after alcohol, was significantly larger than the one obtained after water (124 +/- 17 vs. 57 +/- 8; P < 0.01). Similar insulin and glucose levels were obtained after alcohol and water. Group II serum leptin levels increased after both alcohol and water during the initial part of the night (18.00-20.00 hours). In this period alcohol inhibited the secretion of leptin as shown by the leptin incremental area (AUC18-24) which was 53 +/- 18 after alcohol and 113 +/- 15 after water (P < 0.01). As the ethanol concentration in serum began to fall, its inhibitory effect on leptin gradually disappeared, and when leptin AUCs representing the entire night were determined after alcohol and water, they were not significantly different. Similar insulin, glucose, testosterone, IGF-1 and cortisol levels were found after alcohol and water. The IGFBP-1 level increased, but not significantly so until 6 h after commencing the alcohol ingestion.


CONCLUSIONS
Ingestion of moderate amounts of alcohol has an inhibitory effect on leptin secretion in normal subjects. The effect may be direct rather than indirect, since several factors known to affect leptin are not influenced by alcohol. It is tempting to speculate that alcohol might serve as an appetizer by decreasing leptin secretion, but additional studies are necessary to prove that hypothesis since previous studies have shown that leptin has a long-term rather than an acute effect on hunger.
Röjdmark
S
S
Karolinska Institute, Department of Endocrinology and Diabetology, Karolinska Hospital, Stockholm, Sweden. sven.rojdmark@medklin.sos.sll.se
Calissendorff
J
J
Brismar
K
K
D000284:Administration, Oral; D000328:Adult; D000428:Alcohol Drinking; D000704:Analysis of Variance; D019540:Area Under Curve; D001786:Blood Glucose / Q000032:analysis; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002940:Circadian Rhythm; D003864:Depression, Chemical; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D020738:Leptin / Q000097:blood / Q000378:metabolism*; D008297:Male; D013739:Testosterone / Q000097:blood
D001786:Blood Glucose; D002492:Central Nervous System Depressants; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D020738:Leptin; D000431:Ethanol; D013739:Testosterone; D007334:Insulin-Like Growth Factor I; D006854:Hydrocortisone