title: Treatment of obese subjects with the oral growth hormone secretagogue MK-677 affects serum concentrations of several lipoproteins, but not lipoprotein(a).
abstract: Obesity is associated with blunted GH secretion and an unfavorable lipoprotein pattern. The objective of this study was to investigate the effects of treatment with the oral GH secretagogue MK-677 on lipoproteins in otherwise healthy obese males. The study was randomized, double blind, and parallel. Twenty-four obese males, aged 18-50 yr, with body mass index greater than 30 kg/m2 and waist/hip ratio above 0.95 were treated with 25 mg MK-677 (n = 12) or placebo (n = 12) daily for 8 weeks. MK-677 treatment did not significantly change serum lipoprotein(a) [Lp(a)] levels. Serum apolipoprotein A-I and E (apoA-I and apoE) were increased at 2 weeks (P < 0.001 and P < 0.01 vs. placebo, respectively), but were not changed at study end. Serum total cholesterol and low density lipoprotein (LDL) cholesterol (LDL-C) levels were not significantly changed by MK-677 treatment. Serum high density lipoprotein (HDL) cholesterol (HDL-C) was increased at 2 weeks of MK-677 treatment (P < 0.01 vs. placebo), but not at 8 weeks. The LDL-C/HDL-C ratio was reduced after 8 weeks of MK-677 treatment (P < 0.05 vs. placebo). Mean LDL particle diameter was decreased at 2 weeks (P < 0.05 vs. placebo), but was unchanged compared with baseline values at 8 weeks (P = NS vs. placebo). The level of serum triglycerides was increased at 2 (P < 0.05 vs. placebo), but not at 8, weeks. Lipoprotein lipase activity in abdominal and gluteal sc adipose tissue was not affected by active treatment. In conclusion, treatment with the oral GH secretagogue MK-677 affected circulating lipoproteins. The effects on serum apoA-1, apoE, triglycerides, and mean LDL particle diameter were transient. At study end, the LDL-C/HDL-C ratio was decreased. MK-677 treatment did not significantly affect serum Lp(a) concentrations at the present dose and administration protocol.
authors.affiliation: Research Center for Endocrinology and Metabolism, Sahlgrenska University Hospital, Göteborg, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Svensson
authors.forename: J O
authors.initials: JO
authors.lastname: Jansson
authors.forename: M
authors.initials: M
authors.lastname: Ottosson
authors.forename: G
authors.initials: G
authors.lastname: Johannsson
authors.forename: M R
authors.initials: MR
authors.lastname: Taskinen
authors.forename: O
authors.initials: O
authors.lastname: Wiklund
authors.forename: B A
authors.initials: BA
authors.lastname: Bengtsson
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001054:Apolipoproteins A / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004032:Diet; D004311:Double-Blind Method; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D017270:Lipoprotein(a) / Q000097:blood*; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000188:drug therapy*; D010316:Particle Size; D013141:Spiro Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
chemical_list: D019440:Anti-Obesity Agents; D001054:Apolipoproteins A; D008078:Cholesterol, LDL; D007211:Indoles; D017270:Lipoprotein(a); D008074:Lipoproteins; D013141:Spiro Compounds; D014280:Triglycerides; D019382:Human Growth Hormone; C094817:ibutamoren mesylate