Effects of lowering circulating free fatty acid levels on protein metabolism in adult growth hormone deficient patients.
Our study was conducted to define the roles of lowering circulating free fatty acids (FFA) and of growth hormone (GH) replacement on protein metabolism in GH deficient patients. To isolate the specific effects of FFA and GH we studied seven adult subjects with GH deficiency four times: (A) with administration of GH and Acipimox (an inhibitor of lipolysis), (B) with GH, without Acipimox, (C) without GH, with Acipimox and (D) without either. Each study included a 3 h basal period and a 3 h euglycemic clamp. Amino acid metabolism was assessed by stable isotope dilution technique at the whole body level and across the forearm. Overall, we saw no intervention effect on protein metabolism, but when the two situations in which Acipimox was given were combined, Acipimox decreased basal plasma FFA concentrations by 75% and increased serum urea concentrations by 20%, whole body appearance rates (reflecting protein degradation) of phenylalanine (by 7%) and tyrosine (by 11%) and protein synthesis rates for phenylalanine (by 7%), whereas phenylalanine-to-tyrosine conversion was unaffected. Acipimox more than doubled net forearm phenylalanine release during the clamp and increased basal forearm phenylalanine disappearance (reflecting muscle protein synthesis). During the clamp whole body amino acid fluxes and phenylalanine-to-tyrosine conversion decreased together with a decrease in forearm protein breakdown. GH replacement did not affect any of these metabolic parameters. Although we failed to show any role for GH, the results show that lowering of FFA concentrations with Acipimox has pronounced effects on protein metabolism, including increased whole body and forearm protein breakdown, together with increased protein synthesis systemically and locally in the forearm. The increase in serum urea and a doubling of net forearm phenylalanine release after lowering of FFA strongly indicate that the overall effect is catabolic and supports a pivotal protein conserving role of lipids.
Nielsen
Steen
S
Medical Department M, Aarhus University Hospital, Aarhus C, Denmark.
Jørgensen
Jens O L
JO
Hartmund
Tore
T
Nørrelund
Helene
H
Nair
K S
KS
Christiansen
Jens Sandahl
JS
Møller
Niels
N
D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D004393:Dwarfism, Pituitary / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D005542:Forearm / Q000098:blood supply; D013006:Growth Hormone / Q000008:administration & dosage / Q000097:blood; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008066:Lipolysis / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010649:Phenylalanine / Q000097:blood; D011506:Proteins / Q000378:metabolism*; D011719:Pyrazines / Q000494:pharmacology; D014443:Tyrosine / Q000097:blood; D014508:Urea / Q000097:blood
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D000960:Hypolipidemic Agents; D011506:Proteins; D011719:Pyrazines; D014443:Tyrosine; D010649:Phenylalanine; D014508:Urea; D013006:Growth Hormone; C027696:acipimox