title: The decisive role of free fatty acids for protein conservation during fasting in humans with and without growth hormone.
abstract: During fasting, a lack of GH increases protein loss by close to 50%, but the underlying mechanisms remain uncertain. The present study tests the hypothesis that the anabolic actions of GH depend on mobilization of lipids. Seven normal subjects were examined on four occasions during a 37-h fast with infusion of somatostatin, insulin, and glucagon for the final 15 h: 1) with GH replacement, 2) with GH replacement and antilipolysis with acipimox, 3) without GH and with antilipolysis, and 4) with GH replacement, antilipolysis, and infusion of intralipid. Urinary urea excretion, serum urea concentrations, and muscle protein breakdown (assessed by labeled phenylalanine) increased by almost 50% during fasting with suppression of lipolysis. Addition of GH during fasting with antilipolysis did not influence indexes of protein degradation, whereas restoration of high FFA levels regenerated proportionally low concentrations of urea and decreased whole body protein degradation (phenylalanine to tyrosine conversion) by 10-15%, but failed to affect muscle protein metabolism. Thus, the present data provide strong evidence that FFA are important protein-sparing agents during fasting. The finding that inhibition of lipolysis eliminates the ability of GH to restrict fasting protein loss indicates that stimulation of lipolysis is the principal protein-conserving mechanism of GH.
authors.affiliation: Medical Department M (Endocrinology and Diabetes), Aarhus University Hospital, DK-8000 Aarhus C, Denmark. helenenorrelund@dadlnet.dk
authors.forename: Helene
authors.initials: H
authors.lastname: Nørrelund
authors.forename: K Sreekumaran
authors.initials: KS
authors.lastname: Nair
authors.forename: Steen
authors.initials: S
authors.lastname: Nielsen
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
authors.forename: Per
authors.initials: P
authors.lastname: Ivarsen
authors.forename: Jens Otto Lunde
authors.initials: JO
authors.lastname: Jørgensen
authors.forename: Jens Sandahl
authors.initials: JS
authors.lastname: Christiansen
authors.forename: Niels
authors.initials: N
authors.lastname: Møller
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000097:blood; D005215:Fasting / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D013006:Growth Hormone / Q000494:pharmacology*; D006493:Heparin / Q000097:blood; D006727:Hormone Antagonists / Q000494:pharmacology; D019382:Human Growth Hormone / Q000097:blood* / Q000502:physiology; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D017551:Microdialysis; D018482:Muscle, Skeletal / Q000378:metabolism; D010649:Phenylalanine / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D011719:Pyrazines / Q000494:pharmacology; D013004:Somatostatin / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism; D014508:Urea / Q000652:urine
chemical_list: D000596:Amino Acids; D005230:Fatty Acids, Nonesterified; D006727:Hormone Antagonists; D000960:Hypolipidemic Agents; D011506:Proteins; D011719:Pyrazines; D014280:Triglycerides; D019382:Human Growth Hormone; D014443:Tyrosine; D010649:Phenylalanine; D013004:Somatostatin; D014508:Urea; D013006:Growth Hormone; D006493:Heparin; C027696:acipimox