Lower Fasted State but Greater Change in Plasma Amino Acid-Induced Rise in Muscle Protein Synthesis in People with Obesity

Objective Obesity alters protein metabolism in skeletal muscle, but consistent evidence is lacking. We compared muscle protein synthesis in adults with obesity to that in lean controls in the fasted state and during an amino acid infusion. Methods Ten subjects with obesity (age 36 ± 3 years; BMI 34 ± 1 kg/m2) and ten controls (age 35 ± 3 years; BMI 23 ± 1 kg/m2) received an infusion of L-[2,3,3,4,5,5,5,6,6,6-2H10]leucine (0.15 μmol/kg FFM/min) to measure muscle protein synthesis after an overnight fast and during amino acid infusion. Results Despite greater muscle mTOR phosphorylation (P ≤ 0.05), fasted-state mixed-muscle and mitochondrial protein synthesis were lower in subjects with obesity (P ≤ 0.05). However, the change in mixed-muscle protein synthesis during the amino acid infusion was 2.7-fold greater in subjects with obesity (P ≤ 0.05), accompanied by a greater change in S6K1 phosphorylation (P ≤ 0.05). The change in mitochondrial protein synthesis did not differ between groups (P > 0.05). Conclusions Adults with obesity have reduced muscle protein synthesis in the fasted state, but this response is compensated for by a greater change in overall muscle protein synthesis during amino acid infusion.

[1]  S. Paluska,et al.  Protein‐Rich Food Ingestion Stimulates Mitochondrial Protein Synthesis in Sedentary Young Adults of Different BMIs , 2017, The Journal of clinical endocrinology and metabolism.

[2]  Benoit Smeuninx,et al.  Age-Related Anabolic Resistance of Myofibrillar Protein Synthesis Is Exacerbated in Obese Inactive Individuals , 2017, The Journal of clinical endocrinology and metabolism.

[3]  S. Paluska,et al.  Anabolic sensitivity of postprandial muscle protein synthesis to the ingestion of a protein-dense food is reduced in overweight and obese young adults. , 2016, The American journal of clinical nutrition.

[4]  L. Mandarino,et al.  Prolonged Exposure of Primary Human Muscle Cells to Plasma Fatty Acids Associated with Obese Phenotype Induces Persistent Suppression of Muscle Mitochondrial ATP Synthase β Subunit , 2016, PloS one.

[5]  J. Rungby,et al.  Differential regulation of lipid and protein metabolism in obese vs. lean subjects before and after a 72-h fast. , 2016, American journal of physiology. Endocrinology and metabolism.

[6]  W. Willis,et al.  Subsarcolemmal mitochondria isolated with the proteolytic enzyme nagarse exhibit greater protein specific activities and functional coupling , 2016, Biochemistry and biophysics reports.

[7]  B. Mittendorfer,et al.  Sexual dimorphism in skeletal muscle protein turnover. , 2016, Journal of applied physiology.

[8]  M. Livingstone,et al.  Eating Frequency Is Positively Associated with Overweight and Central Obesity in U.S. Adults. , 2015, The Journal of nutrition.

[9]  W. Kraus,et al.  Impact of combined resistance and aerobic exercise training on branched-chain amino acid turnover, glycine metabolism and insulin sensitivity in overweight humans , 2015, Diabetologia.

[10]  L. Roust,et al.  A new method to measure muscle protein synthesis in humans by endogenously introduced d9-leucine and using blood for precursor enrichment determination , 2015, Physiological reports.

[11]  M. Rennie,et al.  Obesity Appears to Be Associated With Altered Muscle Protein Synthetic and Breakdown Responses to Increased Nutrient Delivery in Older Men, but Not Reduced Muscle Mass or Contractile Function , 2015, Diabetes.

[12]  S. Burgos,et al.  Protein and glucose metabolic responses to hyperinsulinemia, hyperglycemia, and hyperaminoacidemia in obese men , 2015, Obesity.

[13]  D. Reeds,et al.  Protein Ingestion Induces Muscle Insulin Resistance Independent of Leucine-Mediated mTOR Activation , 2014, Diabetes.

[14]  C. Morse,et al.  The impact of obesity on skeletal muscle architecture in untrained young vs. old women , 2014, Journal of anatomy.

[15]  K. Nair,et al.  High insulin combined with essential amino acids stimulates skeletal muscle mitochondrial protein synthesis while decreasing insulin sensitivity in healthy humans. , 2014, The Journal of clinical endocrinology and metabolism.

[16]  G. Rizzo,et al.  Influence of body adiposity on structural characteristics of skeletal muscle in men and women , 2014, Clinical physiology and functional imaging.

[17]  M. Lazar,et al.  The Health Risk of Obesity—Better Metrics Imperative , 2013, Science.

[18]  E. Volpi,et al.  Protein metabolism in women and men: similarities and disparities , 2011, Current opinion in clinical nutrition and metabolic care.

[19]  M. Rennie,et al.  Muscle full effect after oral protein: time-dependent concordance and discordance between human muscle protein synthesis and mTORC1 signaling. , 2010, The American journal of clinical nutrition.

[20]  M. Jensen,et al.  Rapid measurement of plasma free fatty acid concentration and isotopic enrichment using LC/MS , 2010, Journal of Lipid Research.

[21]  L. Mandarino,et al.  Increased Reactive Oxygen Species Production and Lower Abundance of Complex I Subunits and Carnitine Palmitoyltransferase 1B Protein Despite Normal Mitochondrial Respiration in Insulin-Resistant Human Skeletal Muscle , 2010, Diabetes.

[22]  K. Esser,et al.  Anabolic and catabolic pathways regulating skeletal muscle mass , 2010, Current opinion in clinical nutrition and metabolic care.

[23]  Benjamin P. Bowen,et al.  Proteomics Analysis of Human Skeletal Muscle Reveals Novel Abnormalities in Obesity and Type 2 Diabetes , 2009, Diabetes.

[24]  S. Walrand,et al.  Changes in basal and insulin and amino acid response of whole body and skeletal muscle proteins in obese men. , 2009, The Journal of clinical endocrinology and metabolism.

[25]  M. Beydoun,et al.  Meat consumption is associated with obesity and central obesity among US adults , 2009, International Journal of Obesity.

[26]  Kjell Torén,et al.  Eating patterns and portion size associated with obesity in a Swedish population , 2009, Appetite.

[27]  M. Rennie,et al.  Disassociation between the effects of amino acids and insulin on signaling, ubiquitin ligases, and protein turnover in human muscle , 2008, American journal of physiology. Endocrinology and metabolism.

[28]  T. Byers,et al.  Diet composition and risk of overweight and obesity in women living in the southwestern United States. , 2007, Journal of the American Dietetic Association.

[29]  R. Wolfe The underappreciated role of muscle in health and disease. , 2006, The American journal of clinical nutrition.

[30]  G. Thomas,et al.  Nutrient overload, insulin resistance, and ribosomal protein S6 kinase 1, S6K1. , 2006, Cell metabolism.

[31]  C. Lafortuna,et al.  Gender variations of body composition, muscle strength and power output in morbid obesity , 2005, International Journal of Obesity.

[32]  T. Trappe,et al.  Human soleus and vastus lateralis muscle protein metabolism with an amino acid infusion. , 2005, American journal of physiology. Endocrinology and metabolism.

[33]  A. Juul Serum levels of insulin-like growth factor I and its binding proteins in health and disease. , 2003, Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society.

[34]  D. Hood,et al.  PPARgamma coactivator-1alpha expression during thyroid hormone- and contractile activity-induced mitochondrial adaptations. , 2003, American journal of physiology. Cell physiology.

[35]  L. Lissner,et al.  Meal patterns and obesity in Swedish women–a simple instrument describing usual meal types, frequency and temporal distribution , 2002, European Journal of Clinical Nutrition.

[36]  R. Ross,et al.  Estimation of skeletal muscle mass by bioelectrical impedance analysis. , 2000, Journal of applied physiology.

[37]  K. Yarasheski,et al.  Resistance exercise acutely increases MHC and mixed muscle protein synthesis rates in 78-84 and 23-32 yr olds. , 2000, American journal of physiology. Endocrinology and metabolism.

[38]  M. Matsuda,et al.  Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. , 1999, Diabetes care.

[39]  R. Marcus,et al.  Effect of rhGH and rhIGF-I treatment on protein utilization in elderly women. , 1997, The American journal of physiology.

[40]  佐守 友博,et al.  IGF-1 (insulin like growth factor-1) 測定の臨床的意義 , 1995 .

[41]  D. Fryburg Insulin-like growth factor I exerts growth hormone- and insulin-like actions on human muscle protein metabolism. , 1994, The American journal of physiology.

[42]  G. Forbes,et al.  Lean body mass in obesity. , 1983, International journal of obesity.

[43]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.