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Dose-response effects of free fatty acids on amino acid metabolism and ureagenesis.
Acta Physiol (Oxf). 2008 Mar; 192(3):369-79.AP

Abstract

AIM

Free fatty acids (FFAs) are important fuels and have vital protein-sparing effects, particularly during conditions of metabolic stress and fasting. However, it is uncertain whether these beneficial effects are evident throughout the physiological range or only occur at very high FFA concentrations. It is also unclear whether secondary alterations in hormone levels and ketogenesis play a role. We therefore aimed at describing dose-response relationships between amino acid metabolism and circulating FFA concentrations at clamped hormone levels.

METHODS

Eight healthy men were studied on four occasions (6 h basal, 2 h glucose clamp). Endogenous lipolysis was blocked with acipimox and Intralipid was infused at varying rates (0, 3, 6 or 12 microL kg(-1) min(-1)) to obtain four different levels of circulating FFAs. Endogenous growth hormone, insulin and glucagon secretion was blocked by somatostatin (300 microg h(-1)) and replaced exogenously. 15N-phenylalanine, 2H4-tyrosine and 13C-urea were infused continuously to assess protein turnover and ureagenesis.

RESULTS

We obtained four distinct levels of FFA concentrations ranging from 0.03 to 2.1 mmol L(-1) and 3-hydroxybutyrate concentrations from 10 to 360 micromol L(-1). Whole-body phenylalanine turnover and phenylalanine-to-tyrosine degradation decreased with increasing FFA levels as did insulin-stimulated forearm fluxes of phenylalanine. Phenylalanine, tyrosine and urea concentrations also decreased progressively, whereas urea turnover was unperturbed.

CONCLUSION

Circulating FFAs decrease amino acid concentrations and inhibit whole-body phenylalanine fluxes and phenylalanine-to-tyrosine conversion. Our data cover FFA concentrations from 0 to 2 mmol L(-1) and indicate that FFAs exert their protein conserving effects in the upper physiological range (>1.5 mmol L(-1)).

Authors+Show Affiliations

Medical Department M (Endocrinology & Diabetes), Aarhus University Hospital, Aarhus, Denmark. lars.christian.gormsen@ki.au.dkNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17973949

Citation

Gormsen, L C., et al. "Dose-response Effects of Free Fatty Acids On Amino Acid Metabolism and Ureagenesis." Acta Physiologica (Oxford, England), vol. 192, no. 3, 2008, pp. 369-79.
Gormsen LC, Gjedsted J, Gjedde S, et al. Dose-response effects of free fatty acids on amino acid metabolism and ureagenesis. Acta Physiol (Oxf). 2008;192(3):369-79.
Gormsen, L. C., Gjedsted, J., Gjedde, S., Nørrelund, H., Christiansen, J. S., Schmitz, O., Jørgensen, J. O., & Møller, N. (2008). Dose-response effects of free fatty acids on amino acid metabolism and ureagenesis. Acta Physiologica (Oxford, England), 192(3), 369-79.
Gormsen LC, et al. Dose-response Effects of Free Fatty Acids On Amino Acid Metabolism and Ureagenesis. Acta Physiol (Oxf). 2008;192(3):369-79. PubMed PMID: 17973949.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dose-response effects of free fatty acids on amino acid metabolism and ureagenesis. AU - Gormsen,L C, AU - Gjedsted,J, AU - Gjedde,S, AU - Nørrelund,H, AU - Christiansen,J S, AU - Schmitz,O, AU - Jørgensen,J O L, AU - Møller,N, Y1 - 2007/10/31/ PY - 2007/11/2/pubmed PY - 2008/3/14/medline PY - 2007/11/2/entrez SP - 369 EP - 79 JF - Acta physiologica (Oxford, England) JO - Acta Physiol (Oxf) VL - 192 IS - 3 N2 - AIM: Free fatty acids (FFAs) are important fuels and have vital protein-sparing effects, particularly during conditions of metabolic stress and fasting. However, it is uncertain whether these beneficial effects are evident throughout the physiological range or only occur at very high FFA concentrations. It is also unclear whether secondary alterations in hormone levels and ketogenesis play a role. We therefore aimed at describing dose-response relationships between amino acid metabolism and circulating FFA concentrations at clamped hormone levels. METHODS: Eight healthy men were studied on four occasions (6 h basal, 2 h glucose clamp). Endogenous lipolysis was blocked with acipimox and Intralipid was infused at varying rates (0, 3, 6 or 12 microL kg(-1) min(-1)) to obtain four different levels of circulating FFAs. Endogenous growth hormone, insulin and glucagon secretion was blocked by somatostatin (300 microg h(-1)) and replaced exogenously. 15N-phenylalanine, 2H4-tyrosine and 13C-urea were infused continuously to assess protein turnover and ureagenesis. RESULTS: We obtained four distinct levels of FFA concentrations ranging from 0.03 to 2.1 mmol L(-1) and 3-hydroxybutyrate concentrations from 10 to 360 micromol L(-1). Whole-body phenylalanine turnover and phenylalanine-to-tyrosine degradation decreased with increasing FFA levels as did insulin-stimulated forearm fluxes of phenylalanine. Phenylalanine, tyrosine and urea concentrations also decreased progressively, whereas urea turnover was unperturbed. CONCLUSION: Circulating FFAs decrease amino acid concentrations and inhibit whole-body phenylalanine fluxes and phenylalanine-to-tyrosine conversion. Our data cover FFA concentrations from 0 to 2 mmol L(-1) and indicate that FFAs exert their protein conserving effects in the upper physiological range (>1.5 mmol L(-1)). SN - 1748-1716 UR - https://www.unboundmedicine.com/medline/citation/17973949/Dose_response_effects_of_free_fatty_acids_on_amino_acid_metabolism_and_ureagenesis_ DB - PRIME DP - Unbound Medicine ER -