Forearm and leg amino acid metabolism in the basal state and during combined insulin and amino acid stimulation after a 3‐day fast

Gjedsted, Jakob; Gormsen, Lars Christian; Buhl, Mie; Nørrelund, Helene; Schmitz, Ole; Keiding, Susanne; Tønnesen, Else; Møller, Niels

doi:10.1111/j.1748-1716.2009.02009.x

Cited by 4 publications

(2 citation statements)

References 38 publications

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“…In the present study net phenylalanine release was increased maybe due to decreased protein synthesis. In contrast, others have failed to demonstrate these changes in regional protein metabolism [6], [51]. In present study the combination and concordance of tracer kinetics and measurements of myocellular signaling therefore further strengthens our understanding of fasting induced skeletal muscle wasting.…”

Section: Discussionsupporting

confidence: 79%

Fasting Increases Human Skeletal Muscle Net Phenylalanine Release and This Is Associated with Decreased mTOR Signaling

et al. 2014

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AimFasting is characterised by profound changes in energy metabolism including progressive loss of body proteins. The underlying mechanisms are however unknown and we therefore determined the effects of a 72-hour-fast on human skeletal muscle protein metabolism and activation of mammalian target of rapamycin (mTOR), a key regulator of cell growth.MethodsEight healthy male volunteers were studied twice: in the postabsorptive state and following 72 hours of fasting. Regional muscle amino acid kinetics was measured in the forearm using amino acid tracers. Signaling to protein synthesis and breakdown were assessed in skeletal muscle biopsies obtained during non-insulin and insulin stimulated conditions on both examination days.ResultsFasting significantly increased forearm net phenylalanine release and tended to decrease phenylalanine rate of disappearance. mTOR phosphorylation was decreased by ∼50% following fasting, together with reduced downstream phosphorylation of 4EBP1, ULK1 and rpS6. In addition, the insulin stimulated increase in mTOR and rpS6 phosphorylation was significantly reduced after fasting indicating insulin resistance in this part of the signaling pathway. Autophagy initiation is in part regulated by mTOR through ULK1 and fasting increased expression of the autophagic marker LC3B-II by ∼30%. p62 is degraded during autophagy but was increased by ∼10% during fasting making interpretation of autophagic flux problematic. MAFbx and MURF1 ubiquitin ligases remained unaltered after fasting indicating no change in protesomal protein degradation.ConclusionsOur results show that during fasting increased net phenylalanine release in skeletal muscle is associated to reduced mTOR activation and concomitant decreased downstream signaling to cell growth.

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Section: Discussionsupporting

confidence: 79%

Fasting Increases Human Skeletal Muscle Net Phenylalanine Release and This Is Associated with Decreased mTOR Signaling

et al. 2014

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“…To minimize rapid dilution of the [ h. All the tracers were prepared under sterile conditions and were tested free of bacteria and pyrogens before use. Phenylalanine, urea, and tyrosine kinetics were calculated as previously described (22).…”

Section: Subjectsmentioning

confidence: 99%

Erythropoietin administration acutely stimulates resting energy expenditure in healthy young men

Christensen

Vendelbo

Krusenstjerna-Hafstrøm

et al. 2012

Journal of Applied Physiology

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Treatment with recombinant human erythropoietin (rHuEpo) improves insulin sensitivity in patients with end-stage renal disease, and animal studies indicate that Epo increases fat oxidation. However, the metabolic effects of rHuEpo have never been experimentally studied in healthy humans. The aim was to investigate the effects of an acute rHuEpo bolus on substrate metabolism and insulin sensitivity in healthy young men. Ten healthy young men were studied in a single-blinded, randomized crossover design with a 2-wk washout period receiving 400 IU/kg rHuEpo or placebo. Substrate metabolism was evaluated by indirect calorimetry and tracer infusions, and insulin sensitivity by a hyperinsulinemic euglycemic clamp; and PCR and Western blotting measured protein expression and content, respectively. Resting energy expenditure (REE) increased significantly after rHuEpo [basal: 1,863.3 ± 67.2 (kcal/day) (placebo) vs. 2,041.6 ± 81.2 (rHuEpo), P < 0.001; clamp: 1,903.9 ± 68.3 (placebo) vs. 2,015.7 ± 114.4 (rHuEpo), P = 0.03], but the increase could not be explained by changes in mRNA levels of uncoupling protein 2 or 3. Fat oxidation in the basal state tended to be higher after rHuEpo but could not be explained by changes in mRNA levels of CPT1 and PPARα or AMPK and ACC protein phosphorylation. Insulin-stimulated glucose disposal, glucose metabolism, and whole body and forearm protein metabolism did not change significantly in response to rHuEpo. In conclusion, a single injection of rHuEpo acutely increases REE in healthy human subjects. This calorigenic effect is not accompanied by distinct alterations in the pattern of substrate metabolism or insulin sensitivity.

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Physiological responses to acute fasting: implications for intermittent fasting programs

et al. 2021

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Intermittent fasting (IF) is a dietary strategy that involves alternating periods of abstention from calorie consumption with periods of ad libitum food intake. There is significant interest in the body of literature describing longitudinal adaptations to IF. Less attention has been given to the acute physiological responses that occur during the fasting durations that are commonly employed by IF practitioners. Thus, the purpose of this review was to examine the physiological responses – including alterations in substrate metabolism, systemic hormones, and autophagy – that occur throughout an acute fast. Literature searches were performed to locate relevant research describing physiological responses to acute fasting and short-term starvation. A single fast demonstrated the ability to alter glucose and lipid metabolism within the initial 24 hours, but variations in protein metabolism appeared to be minimal within this time frame. The ability of an acute fast to elicit significant increases in autophagy is still unknown. The information summarized in this review can be used to help contextualize existing research and better inform development of future IF interventions.

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Forearm and leg amino acid metabolism in the basal state and during combined insulin and amino acid stimulation after a 3‐day fast

Cited by 4 publications

References 38 publications

Fasting Increases Human Skeletal Muscle Net Phenylalanine Release and This Is Associated with Decreased mTOR Signaling

Fasting Increases Human Skeletal Muscle Net Phenylalanine Release and This Is Associated with Decreased mTOR Signaling

Erythropoietin administration acutely stimulates resting energy expenditure in healthy young men

Physiological responses to acute fasting: implications for intermittent fasting programs

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