Muscle Protein Synthesis and Balance Responsiveness to Essential Amino Acids Ingestion in the Presence of Elevated Plasma Free Fatty Acid Concentrations

Katsanos, Christos S.; Aarsland, Asle; Cree, Melanie G.; Wolfe, Robert R.

doi:10.1210/jc.2008-2686

Cited by 36 publications

(34 citation statements)

References 43 publications

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“…This is, to our knowledge, the first study to acutely induce anabolic resistance in humans by lipid administration. However, these findings are in contrast to the study of Katsanos et al (22), where lipid was intravenously administered at nearly twice the rate and no blunting of the 50% increase in muscle protein synthesis was observed in response to the ingestion of 7 g essential amino acids. The differences are difficult to reconcile but may be due to the hyperinsulinemic-euglycemic clamp in the current study, which likely impaired fat oxidation and caused an accumulation of intracellular lipid metabolites (23).…”

Section: Discussioncontrasting

confidence: 93%

Lipid-Induced Insulin Resistance Is Associated With an Impaired Skeletal Muscle Protein Synthetic Response to Amino Acid Ingestion in Healthy Young Men

et al. 2014

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The ability to maintain skeletal muscle mass appears to be impaired in insulin resistant conditions. The present study investigated the effect of lipid induced insulin resistance on the rate of muscle protein synthesis. Seven healthy male volunteers (23 ± 1 y, 24 ± 1 kg/m2) underwent a 7 h intravenous infusion of [ring‐2H5]phenylalanine (0.5 mg/kg/h) on two randomised occasions combined with either 0.9% saline or 10% Intralipid (100 mL/h; Fresenius Kabi, Germany). After a 4 h ‘basal’ period, a 21 g bolus of amino acids (except phenylalanine and tyrosine) was administered in a 440 mL solution nasogastrically, and a 3 h euglycaemic (4.5 mmol/L) hyperinsulinemic (50 mU/m2/min) clamp was commenced (‘fed’ period). Muscle biopsies were obtained from the vastus lateralis at 1.5, 4, and 7 h. Lipid infusion resulted in elevated levels of plasma free fatty acids when compared to saline (P<0.001), which reduced fed glucose disposal by 20% (P<0.01) and pyruvate dehydrogenase complex activation by 50% (P<0.05). Furthermore, whereas mixed muscle fractional synthetic rate increased from the basal to fed period during saline infusion (0.040 ± 0.010 to 0.067 ± 0.013 %/h; P<0.05), it did not respond during lipid infusion (0.048 ± 0.013 to 0.038 ± 0.005 %/h), despite the same circulating insulin and leucine concentrations. Thus, lipid induced insulin resistance results in anabolic resistance to amino acid ingestion in healthy young men.

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Section: Discussioncontrasting

confidence: 93%

Lipid-Induced Insulin Resistance Is Associated With an Impaired Skeletal Muscle Protein Synthetic Response to Amino Acid Ingestion in Healthy Young Men

et al. 2014

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“…The effects of increasing FFA availability on direct (Katsanos et al, 2009;Stephens et al, 2014) or indirect (Ferrannini et al, 1986;Gormsen et al, 2008) measures of MPS have also been studied in humans. Katsanos and colleagues (2009) reported little attenuation of MPS in response to the ingestion of 7 g of EAAs after the initiation of a 10 h intralipid infusion (20% Liposyn, 90 ml h −1 ).…”

Section: Increased Fat Availabilitymentioning

confidence: 99%

Effects of skeletal muscle energy availability on protein turnover responses to exercise

Smiles

Hawley

Camera

2016

Journal of Experimental Biology

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Skeletal muscle adaptation to exercise training is a consequence of repeated contraction-induced increases in gene expression that lead to the accumulation of functional proteins whose role is to blunt the homeostatic perturbations generated by escalations in energetic demand and substrate turnover. The development of a specific 'exercise phenotype' is the result of new, augmented steady-state mRNA and protein levels that stem from the training stimulus (i.e. endurance or resistance based). Maintaining appropriate skeletal muscle integrity to meet the demands of training (i.e. increases in myofibrillar and/or mitochondrial protein) is regulated by cyclic phases of synthesis and breakdown, the rate and turnover largely determined by the protein's half-life. Cross-talk among several intracellular systems regulating protein synthesis, breakdown and folding is required to ensure protein equilibrium is maintained. These pathways include both proteasomal and lysosomal degradation systems (ubiquitin-mediated and autophagy, respectively) and the protein translational and folding machinery. The activities of these cellular pathways are bioenergetically expensive and are modified by intracellular energy availability (i.e. macronutrient intake) and the 'training impulse' (i.e. summation of the volume, intensity and frequency). As such, exercisenutrient interactions can modulate signal transduction cascades that converge on these protein regulatory systems, especially in the early post-exercise recovery period. This review focuses on the regulation of muscle protein synthetic response-adaptation processes to divergent exercise stimuli and how intracellular energy availability interacts with contractile activity to impact on muscle remodelling.

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“…A decrease in the activity of the insulin signaling cascade as a result of fatty acid load would be expected to attenuate the insulin-induced response to protein synthesis via the downstream protein kinase B (also known as AKt) and target of rapamycin signaling pathway. However, the data of Katsanos et al (1) showed that even in the presence of fatty acid-induced insulin resistance, the protein synthesis response to amino acid load was not impaired. Studies in healthy humans have shown that amino acids stimulate skeletal muscle protein synthesis through an AKt-independent pathway (11,20).…”

mentioning

confidence: 96%

“…By using isotopic tracers in combination with arteriovenous balance measurements across the leg and by quantifying tracer incorporation into muscle proteins, Katsanos et al (1) have presented a detailed analysis of protein kinetics in the skeletal muscle. As anticipated, increase in plasma free fatty acids resulted in the development of insulin resistance (2).…”

mentioning

confidence: 99%

Fatty Acids, Insulin Resistance, and Protein Metabolism

Kalhan

2009

The Journal of Clinical Endocrinology & Metabolism

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A ccretion and maintenance of lean body mass, because of its fundamental role in health and disease, continues to be an area of intense investigation. By using sophisticated tracer isotopic methods, organ balance techniques, and molecular analysis of tissue samples in humans and animal models, a detailed analysis of the signaling pathway and metabolic fluxes has been possible. Despite these, understanding the regulatory mechanism of nitrogen/protein accretion and maintenance of lean body mass in vivo continues to be challenging. This is particularly difficult because of the adaptation of metabolism to various modifying influences, and because of the multiple levels of regulation in vivo. Yet, by careful studies, a number of investigators have systematically examined the influence of diverse modifiers on the physiology of protein synthesis and breakdown in humans in vivo.In this issue of JCEM, Katsanos et al. have examined, in healthy humans, the impact of elevated plasma fatty acids levels, induced by iv infusion of intralipid and heparin, on the responsiveness of the skeletal muscle protein synthesis and balance to an enterally administered essential amino acid mixture. By using isotopic tracers in combination with arteriovenous balance measurements across the leg and by quantifying tracer incorporation into muscle proteins, Katsanos et al. (1) have presented a detailed analysis of protein kinetics in the skeletal muscle. As anticipated, increase in plasma free fatty acids resulted in the development of insulin resistance (2). Their data show that in the basal state, in the presence of elevated plasma fatty acids levels and insulin resistance, there was a decrease in the rate of appearance of phenylalanine across the leg, suggesting a lower rate of protein breakdown. The rate of disappearance of phenylalanine was not affected, resulting in an improved or less negative amino acid balance. Essential amino acid administration resulted in no change in protein breakdown and caused an increase in phenylalanine rate of disappearance (increase in protein synthesis) and an increase in the fractional rate of protein synthesis. Of significance, fatty acids and/or fatty acid-induced insulin resistance did not impact the rate of protein synthesis by skeletal muscle in response to the amino acid load.Fatty acids are critical oxidative substrates that are mobilized during fasting and result in sparing of glucose and amino acids. Elevated fatty acid levels during fasting are associated with decreased glucose uptake by skeletal muscle, decreased protein breakdown, and a lower rate of protein oxidation and urea synthesis (3). The cause and effect relating fatty acids to changes in fasting metabolism has been examined in a large number of studies. These studies have been done either during fasting when there is a spontaneous increase in plasma fatty acid concentration or by infusing intralipid with heparin, resulting in an increase in the plasma fatty acid levels in the high physiological range. Fatty acids could impact glucose an...

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Muscle Protein Synthesis and Balance Responsiveness to Essential Amino Acids Ingestion in the Presence of Elevated Plasma Free Fatty Acid Concentrations

Abstract: Elevated plasma FFA concentrations do not interfere with the response of muscle protein synthesis and balance to a bolus ingestion of EAAs.

Cited by 36 publications

References 43 publications

Lipid-Induced Insulin Resistance Is Associated With an Impaired Skeletal Muscle Protein Synthetic Response to Amino Acid Ingestion in Healthy Young Men

Lipid-Induced Insulin Resistance Is Associated With an Impaired Skeletal Muscle Protein Synthetic Response to Amino Acid Ingestion in Healthy Young Men

Effects of skeletal muscle energy availability on protein turnover responses to exercise

Fatty Acids, Insulin Resistance, and Protein Metabolism

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