Discrepancy between serum leptin values and total body fat in response to the oral growth hormone secretagogue MK-677.
OBJECTIVE
Growth hormone (GH) treatment decreases total body fat while this effect has not yet been documented for the oral GH secretagogue MK-677. In the present study, the effects of MK-677 treatment on serum levels of leptin, thyroid hormones and testosterone were determined.


METHODS
This was a randomized, double-blind, and parallel study. Twenty-four healthy obese males, 19-49 years of age, with body mass index (BMI) > 30 kg/m2 and a waist:hip ratio > 0.95, were treated with MK-677 (25 mg/day; n = 12) or placebo (n = 12) for 8 weeks.


RESULTS
MK-677 treatment increased serum leptin levels and leptin/body fat ratio at 2 weeks of treatment (P < 0.05 vs. placebo) but no significant change was observed at 8 weeks. An increase in serum free 3, 5, 3'-triiodothyronine (free T3) was not detected until 8 weeks of MK-677 treatment (P < 0.05 vs. placebo). Peak serum thyroid stimulating hormone (TSH) concentration after MK-677 administration was similar to that after placebo administration at initiation of treatment and at 2 weeks. At 8 weeks of MK-677 treatment, mean peak serum TSH concentration was increased (P < 0.05 vs. placebo) although it remained within the normal range. Serum peak values of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were similar after MK-677 and placebo administration. MK-677 treatment reduced serum total testosterone (P < 0.05 vs. placebo) although total testosterone/sex hormone-binding globulin (SHBG) ratio (an index of free testosterone) was not changed.


CONCLUSIONS
Treatment with the oral GH secretagogue MK-677 transiently increased serum leptin levels and leptin/body fat ratio at 2 weeks of treatment, and increased serum free T3 after 8 weeks. These results indicate that MK-677 treatment is able to affect circulating factors of importance for adipose tissue mass and fuel metabolism.
Svensson
J
J
Research Centre for Endocrinology and Metabolism, Sahlgrenska University Hospital, Göteborg, Sweden.
Carlsson
B
B
Carlsson
L M
LM
Jansson
J O
JO
Bengtsson
B A
BA
D000284:Administration, Oral; D000328:Adult; D001823:Body Composition / Q000187:drug effects; D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D020738:Leptin; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D011506:Proteins / Q000378:metabolism*; D013141:Spiro Compounds / Q000627:therapeutic use*; D013739:Testosterone / Q000097:blood; D013972:Thyrotropin / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D002756:Cholagogues and Choleretics; D007211:Indoles; D020738:Leptin; D011506:Proteins; D013141:Spiro Compounds; D014284:Triiodothyronine; D013739:Testosterone; D013972:Thyrotropin; D013006:Growth Hormone; C094817:ibutamoren mesylate