Modulation of the liver export protein synthetic response to feeding by an n−3 fatty-acid-enriched nutritional supplement is associated with anabolism in cachectic cancer patients

2004 ◽  
Vol 106 (4) ◽  
pp. 359-364 ◽  
Author(s):  
Matthew D. BARBER ◽  
Tom PRESTON ◽  
Donald C. McMILLAN ◽  
Christine SLATER ◽  
James A. ROSS ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Fatty Acid ◽  
Fish Oil ◽  
Cancer Patients ◽  
Nutritional Supplement ◽  
Whole Body ◽  
Fasting State ◽  
Fed State ◽  
Export Protein ◽  
Oral Supplement

The acute-phase protein response is associated with accelerated weight loss and shortened survival in cancer. This may be due to hepatic protein synthesis increasing demand for amino acids. An n-3 fatty-acid-enriched nutritional supplement will moderate aspects of cachexia in cancer patients. The present study examined the effect of such a supplement on hepatic synthesis of albumin and fibrinogen. Albumin and fibrinogen synthesis were measured in the fed and fasting state in eight weight-losing patients with pancreatic cancer by an intravenous flooding dose technique. Tracer incorporation into proteins was measured by GC/MS. Patients were restudied after 3 weeks of oral supplement enriched with fish oil (providing 2510 kJ/day and 2 g of eicosapentaenoic acid/day). At baseline, all patients were losing weight (median, 2.4 kg/month). After 3 weeks of consumption of the fish-oil-enriched nutritional supplement, patients′ weight stabilized (median change, +1 kg; P=0.01). At baseline, albumin and fibrinogen synthesis rates were stimulated in the fed compared with the fasting state [14.2 compared with 11.3 g/day (29% rise; P=0.01) and 4.5 compared with 3.3 g/day (38% rise; P=0.01) respectively]. After 3 weeks of the supplement, this stimulation in the fed state was no longer observed for albumin and was reduced for fibrinogen [11.2 compared with 10.5 g/day (3% rise; P=0.21) and 3.7 compared with 2.9 g/day (17% rise; P=0.01) respectively]. After 3 weeks, the combined albumin plus fibrinogen synthetic rate tended to fall in the fasting state (14.7 compared with 12.3 g/day; P=0.09) and was significantly reduced in the fed state (18.7 compared with 14.6 g/day; P=0.01). Modulation of hepatic export protein synthesis with feeding may have contributed to the net whole-body anabolism observed with administration of the n-3 fatty-acid-enriched oral supplement.

Metabolic response to feeding in weight-losing pancreatic cancer patients and its modulation by a fish-oil-enriched nutritional supplement

2000 ◽  
Vol 98 (4) ◽  
pp. 389-399 ◽  
Author(s):  
Matthew D. BARBER ◽  
Donald C. MCMILLAN ◽  
Tom PRESTON ◽  
James A. ROSS ◽  
Kenneth C. H. FEARON
Keyword(s):  
Pancreatic Cancer ◽  
Body Weight ◽  
Energy Expenditure ◽  
Fish Oil ◽  
Cancer Patients ◽  
Metabolic Response ◽  
Resting Energy Expenditure ◽  
Fat Oxidation ◽  
Nutritional Supplement ◽  
Healthy Control

Weight-losing patients with advanced cancer often fail to gain weight with conventional nutritional support. This suboptimal response might be explained, in part, by an increased metabolic response to feeding. It has been suggested that eicosapentaenoic acid (EPA) can modify beneficially the metabolic response to cancer. The aim of the present study was to examine the metabolic response to feeding in cancer and the effects of an EPA-enriched oral food supplement on this response. A total of 16 weight-losing, non-diabetic patients with unresectable pancreatic adenocarcinoma and six healthy, weight-stable controls were studied by indirect calorimetry in the fasting and fed states. Body composition was estimated by bioimpedence analysis. Cancer patients were then given a fish-oil-enriched nutritional supplement providing 2 g of EPA and 2550 kJ daily, and underwent repeat metabolic study after 3 weeks of such supplementation. At baseline, resting energy expenditure whether expressed per kg body weight, lean body mass or body cell mass was significantly greater in the cancer patients compared with controls. Fat oxidation was significantly higher in the fasting state in cancer patients [median 1.26 g·kg-1·min-1 (interquartile range 0.95–1.38)] than in controls [0.76 g·kg-1·min-1 (0.62–0.92); P < 0.05]. Over the 4 h feeding period, changes in insulin and glucose concentrations in cancer patients suggested relative glucose intolerance. In response to oral meal feeding, the percentage change in the area under the curve of energy expenditure was significantly lower in the cancer patients [median 7.9% (interquartile range 3.4–9.0)] than in controls [12.6% (9.9–15.1); P < 0.01]. After 3 weeks of the EPA-enriched supplement, the body weight of the cancer patients had increased and the energy expenditure in response to feeding had risen significantly [9.6% (6.3–12.4)], such that it was no different from baseline healthy control values. Similarly, fasting fat oxidation fell to 1.02 g·kg-1·min-1 (0.8–1.18), again no longer significantly different from baseline healthy control values. While weight-losing patients with advanced pancreatic cancer have an increased resting energy expenditure and increased fat oxidation, the energy cost of feeding is, in fact, reduced. Provision of a fish-oil-enriched nutritional supplement results in some normalization of the metabolic response in both the fasted and fed states, in association with an improvement in nutritional status.

scholarly journals Fed-state clamp stimulates cellular mechanisms of muscle protein anabolism and modulates glucose disposal in normal men

2009 ◽  
Vol 296 (1) ◽  
pp. E105-E113 ◽  
Author(s):  
Olasunkanmi A. J. Adegoke ◽  
Stéphanie Chevalier ◽  
José A. Morais ◽  
Réjeanne Gougeon ◽  
Scot R. Kimball ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Translation Initiation ◽  
Muscle Protein ◽  
Whole Body ◽  
Glucose Disposal ◽  
Metabolic Clearance ◽  
Cellular Mechanisms ◽  
Body Protein ◽  
Fed State ◽  
Mtorc1 Signaling

Since maximum anabolism occurs postprandially, we developed a simulated fed state with clamped hyperinsulinemia, physiological hyperglycemia, and hyperaminoacidemia (Hyper-3) and explored muscle cellular mechanisms. Whole body [1-13C]leucine and [3-3H]glucose kinetics in healthy men were compared between hyperinsulinemic, euglycemic, isoaminoacidemic (Hyper-1, n = 10) and Hyper-3 ( n = 9) clamps. In Hyper-3 vs. Hyper-1, nonoxidative leucine Rd [rate of disappearance (synthesis)] was stimulated more (45 ± 4 vs. 24 ± 4 μmol/min, P < 0.01) and endogenous Ra [rate of appearance (breakdown)] was inhibited similarly; hence net balance increased more (86 ± 6 vs. 49 ± 2 μmol/min, P < 0.001). Glucose Rd was similar; thus Hyper-3 metabolic clearance rate (331 ± 23 vs. 557 ± 41 ml/min, P < 0.0005) and Rd/insulin (M, 0.65 ± 0.10 vs. 1.25 ± 0.10 mg·min−1·pmol−1·l, P < 0.001) were less, despite higher insulin (798 ± 74 vs. 450 ± 24 pmol/l, P < 0.005). In vastus lateralis muscle biopsies, phosphorylation of Akt ( P = 0.025), mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase (p70S6K1; P = 0.008), S6 ( P = 0.049), and 4E-binding protein 1 (4E-BP1; P = 0.001) increased. With decreased eukaryotic initiation factor-4E (eIF4E)·4E-BP1 complex ( P = 0.01), these are consistent with increased mTOR complex 1 (mTORC1) signaling and translation initiation of protein synthesis. Although mRNA expression of ubiquitin, MAFbx 1, and MuRF-1 was unchanged, total ubiquitinated proteins decreased 20% ( P < 0.01), consistent with proteolysis suppression. The Hyper-3 clamp increases whole body protein synthesis, net anabolism, and muscle protein translation initiation pathways and decreases protein ubiquitination. The main contribution of hyperaminoacidemia is stimulation of synthesis rather than inhibition of proteolysis, and it attenuates the expected increment of glucose disposal.

scholarly journals AMPK as a mediator of hormonal signalling

2009 ◽  
Vol 44 (2) ◽  
pp. 87-97 ◽  
Author(s):  
Chung Thong Lim ◽  
Blerina Kola ◽  
Márta Korbonits
Keyword(s):  
Protein Synthesis ◽  
Fatty Acid ◽  
Metabolic Disorders ◽  
Energy Homeostasis ◽  
Metabolic Effects ◽  
Whole Body ◽  
Acid Oxidation ◽  
Treatment Of Obesity ◽  
Amp Activated Protein Kinase ◽  
Hormonal Signalling

AMP-activated protein kinase (AMPK) is a key molecular player in energy homeostasis at both cellular and whole-body levels. AMPK has been shown to mediate the metabolic effects of hormones such as leptin, ghrelin, adiponectin, glucocorticoids and insulin as well as cannabinoids. Generally, activated AMPK stimulates catabolic pathways (glycolysis, fatty acid oxidation and mitochondrial biogenesis) and inhibits anabolic pathways (gluconeogenesis, glycogen, fatty acid and protein synthesis), and has a direct appetite-regulating effect in the hypothalamus. Drugs that activate AMPK, namely metformin and thiazolidinediones, are often used to treat metabolic disorders. Thus, AMPK is now recognised as a potential target for the treatment of obesity and associated co-morbidities.

Fish Oil Decreases C-Reactive Protein/Albumin Ratio Improving Nutritional Prognosis and Plasma Fatty Acid Profile in Colorectal Cancer Patients

Lipids ◽  
2013 ◽  
Vol 48 (9) ◽  
pp. 879-888 ◽  
Author(s):  
Michel Carlos Mocellin ◽  
Juliana de Aguiar Pastore e Silva ◽  
Carolina de Quadros Camargo ◽  
Maria Emília de Souza Fabre ◽  
Scheila Gevaerd ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fatty Acid ◽  
Fish Oil ◽  
Cancer Patients ◽  
Fatty Acid Profile ◽  
Plasma Fatty Acid ◽  
C Reactive Protein ◽  
Albumin Ratio ◽  
Reactive Protein ◽  
Colorectal Cancer Patients

The Fed-State Clamp Increases Whole-Body Protein Anabolism by Activation of Plasma and Muscle Protein Synthesis, in Healthy Men

2008 ◽  
Vol 32 (4) ◽  
pp. 341
Author(s):  
Stéphanie Chevalier ◽  
Olasunkanmi A.J. Adegoke ◽  
Linda Wykes ◽  
José A. Morais ◽  
Réjeanne Gougeon ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Whole Body ◽  
Body Protein ◽  
Fed State ◽  
Healthy Men

scholarly journals Peak Fat Oxidation Rate Is Closely Associated With Plasma Free Fatty Acid Concentrations in Women; Similar to Men

2021 ◽  
Vol 12 ◽  
Author(s):  
Jacob Frandsen ◽  
Axel Illeris Poggi ◽  
Christian Ritz ◽  
Steen Larsen ◽  
Flemming Dela ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Plasma Free Fatty Acid ◽  
Fat Oxidation ◽  
Whole Body ◽  
Men And Women ◽  
Fed State ◽  
Repeated Exercise ◽  
Graded Exercise ◽  
Plasma Ffa

Introduction: In men, whole body peak fat oxidation (PFO) determined by a graded exercise test is closely tied to plasma free fatty acid (FFA) availability. Men and women exhibit divergent metabolic responses to fasting and exercise, and it remains unknown how the combined fasting and exercise affect substrate utilization in women. We aimed to investigate this, hypothesizing that increased plasma FFA concentrations in women caused by fasting and repeated exercise will increase PFO during exercise. Then, that PFO would be higher in women compared with men (data from a previous study).Methods: On two separate days, 11 young endurance-trained women were investigated, either after an overnight fast (Fast) or 3.5 h after a standardized meal (Fed). On each day, a validated graded exercise protocol (GXT), used to establish PFO by indirect calorimetry, was performed four times separated by 3.5 h of bed rest both in the fasted (Fast) or fed (Fed) state.Results: Peak fat oxidation increased in the fasted state from 11 ± 3 (after an overnight fast, Fast 1) to 16 ± 3 (mean ± SD) mg/min/kg lean body mass (LBM) (after ~22 h fast, Fast 4), and this was highly associated with plasma FFA concentrations, which increased from 404 ± 203 (Fast 1) to 865 ± 210 μmol/L (Fast 4). No increase in PFO was found during the fed condition with repeated exercise. Compared with trained men from a former identical study, we found no sex differences in relative PFO (mg/min/kg LBM) between men and women, in spite of significant differences in plasma FFA concentrations during exercise after fasting.Conclusion: Peak fat oxidation increased with fasting and repeated exercise in trained women, but the relative PFO was similar in young trained men and women, despite major differences in plasma lipid concentrations during graded exercise.

Advances in stable isotope tracer methodology part 2: new thoughts about an “old” method—measurement of whole body protein synthesis and breakdown in the fed state

2019 ◽  
Vol 68 (1) ◽  
pp. 11-15 ◽  
Author(s):  
Robert R Wolfe ◽  
Sanghee Park ◽  
Il-Young Kim ◽  
Paul J Moughan ◽  
Arny A Ferrando
Keyword(s):  
Protein Synthesis ◽  
Dietary Protein ◽  
Protein Turnover ◽  
Peripheral Circulation ◽  
Whole Body ◽  
Balance Model ◽  
Body Protein ◽  
Fed State ◽  
Isotope Tracer ◽  
Tracer Dilution

Whole-body protein turnover (protein synthesis, breakdown, and net balance) model enables quantification of the response to a variety of circumstances, including the response to meal feeding. In the fed state, the whole-body protein turnover model requires taking account of the contribution of absorbed tracee to the observed total appearance of tracee in the peripheral blood (exogenous appearance, RaEXO). There are different approaches to estimating RaEXO. The use of an intrinsically labeled dietary protein is based on the overriding assumption that the appearance in the peripheral circulation of a tracer amino acid incorporated into a dietary protein is exactly proportional to the appearance of absorbed tracee. The bioavailability approach is based on the true ileal digestibility of the dietary protein and the irreversible loss of the tracee in the splanchnic bed via hydroxylation of the tracee (phenylalanine). Finally, RaEXO can be estimated as the increase above the basal rate of appearance of the tracee using traditional tracer dilution methodology. In this paper, we discuss the pros and cons of each approach and conclude that the bioavailability method is the least likely to introduce systematic errors and is therefore the preferable approach.

Whole body protein metabolism and resting energy expenditure in pregnant Gambian women

1992 ◽  
Vol 263 (4) ◽  
pp. E624-E631 ◽  
Author(s):  
L. Willommet ◽  
Y. Schutz ◽  
R. Whitehead ◽  
E. Jequier ◽  
E. B. Fern
Keyword(s):  
Protein Synthesis ◽  
Energy Expenditure ◽  
Protein Metabolism ◽  
Resting Energy Expenditure ◽  
First Trimester ◽  
Significant Rise ◽  
Whole Body ◽  
Body Protein ◽  
Fed State ◽  
Resting Energy

Whole body protein metabolism and resting energy expenditure (REE) were measured at 11, 23, and 33 wk of pregnancy in nine pregnant (not malnourished) Gambian women and in eight matched nonpregnant nonlactating (NPNL) matched controls. Rates of whole body nitrogen flux, protein synthesis, and protein breakdown were determined in the fed state from the level of isotope enrichment of urinary urea and ammonia during a period of 9 h after a single oral dose of [15N]glycine. At regular intervals, REE was measured by indirect calorimetry (hood system). Based on the arithmetic end-product average of values obtained with urea and ammonia, a significant increase in whole body protein synthesis was observed during the second trimester (5.8 +/- 0.4 g.kg-1.day-1) relative to values obtained both for the NPNL controls (4.5 +/- 0.3 g.kg-1.day-1) and those during the first trimester (4.7 +/- 0.3 g.kg-1.day-1). There was a significant rise in REE during the third trimester both in the preprandial and postprandial states. No correlation was found between REE after meal ingestion and the rate of whole body protein synthesis.

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