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The Decisive Role of Free Fatty Acids for Protein Conservation during Fasting in Humans with and without Growth Hormone

Medical Department M (Endocrinology and Diabetes) (H.N., S.N., J.O.L.J., J.S.C.), Institute of Experimental Clinical Research (J.F., N.M.), Department of Nephrology (P.I.), Aarhus University Hospital, DK-8000 Aarhus C, Denmark; and Endocrinology Division, Mayo Clinic (K.S.N.), Rochester, Minnesota 55905

Address all correspondence and requests for reprints to: Dr. Helene Nørrelund, Medical Department M, Aarhus Kommunehospital, DK-8000 Aarhus C, Denmark. E-mail: helenenorrelund{at}dadlnet.dk.

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.

This work was supported by Novo Nordisk Fonden, Aage and Johanne Louis-Hansens Fond, the Danish Research Council, Grant 9600822 (Novo Nordisk Center for Research in Growth and Regeneration, Aarhus University), and NIH Grants RO1-DK-41973 and RR-00585.

Abbreviations: FFA, Free fatty acids; GHDA, GH-deficient adults; 3-OH-butyrate, 3-hydroxybutyrate; TBW, total body water; UNSR, urea-nitrogen synthesis rate.

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