Additional Files

Giacco, A., Silvestri, E., Senese, R., Cioffi, F., Cuomo, A., Lombardi, A., Moreno, M., Lanni, A., & de Lange, P. . (2021). Exercise with Energy Restriction as a Means of Losing Body Mass while Preserving Muscle Quality and Ameliorating Co-morbidities: Towards a Therapy for Obesity?. Translational Medicine and Exercise Prescription, 1(1), 13–24. https://doi.org/10.53941/tmep.v1i1.31

Exercise with Energy Restriction as a Means of Losing Body Mass while Preserving Muscle Quality and Ameliorating Co-morbidities: Towards a Therapy for Obesity?

Antonia Giacco1*, Elena Silvestri1*, Rosalba Senese2, Federica Cioffi1, Arianna Cuomo2, Assunta Lombardi3, Maria Moreno1, Antonia Lanni2 and Pieter de Lange()2 

1Dipartimento di Science e Tecnologie, Università degli Studi del Sannio, Benevento, Italy

2Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Università degli Studi della Campania "Luigi Vanvitelli," Caserta, Italy

3Dipartimento di Biologia, Università degli Studi di Napoli "Federico II," Napoli, Italy

© The Authors


 

Abstract

Obesity and related co-morbidities are a major public health threat worldwide, and efforts to counteract obesity by means of physiological interventions are currently being explored and applied. Here we present an overview of the literature on the effect of dietary/exercise-based programs on loss of different components of body mass. We also discuss gain or lack of loss of lean mass in view of muscle quality maintenance, which is an important aspect to consider when employing weight-loss strategies to tackle obesity. By comparing results obtained in participants with mild to severe obesity with those obtained in lean participants, we highlight variations in the success of these interventions. Furthermore, we briefly address the observation that although certain interventions may not always affect body composition they can nevertheless ameliorate co-morbidities (insulin resistance, non-alcoholic fatty liver disease). Based on what is currently known, in this narrative review we include data from human and animal studies related to the process of unravelling the mechanisms underlying conservation of functional muscle mass.

exercise nutritional interventions body composition metabolic co-morbidities obesity

References

  1. Wang HH, Lee DK, Liu M, Portincasa P, Wang DQ. Novel insights into the pathogenesis and management of the metabolic syndrome. Pediatr Gastroenterol Hepatol Nutr 2020, 23: 189-230. https://doi.org/10.5223/pghn.2020.23.3.189
  2. NCD Risk Factor Collaboration (NCD-RisC). Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 populationbased measurement studies with 19.2 million participants. The Lancet 2016, 387: 1377-96. https://doi.org/10.1016/S0140-6736(16)30054-X
  3. Ishizaki T, Watanabe S, Suzuki T, Shibata H, Haga H. Predictors for functional decline among nondisabled older Japanese living in a community during a 3-year follow-up. J Am Geriatr Soc 2000, 48: 1424-29.
    https://doi.org/10.1111/j.1532-5415.2000.tb02632.x
  4. Hicks GE, Shardell M, Alley DE, Miller RR, Bandinelli S, Guralnik J, Lauretani F, Simonsick EM, Ferrucci L. Absolute strength and loss of strength as predictors of mobility decline in older adults: the InCHIANTI study. J Gerontol A Biol Sci Med Sci 2012, 67: 66-73. https://doi.org/10.1093/gerona/glr055
  5. Clark DJ, Patten C, Reid KF, Carabello RJ, Phillips EM, Fielding RA. Impaired voluntary neuromuscular activation limits muscle power in mobility-limited older adults. J Gerontol A Biol Sci Med Sci 2010, 65: 495-502. https://doi.org/10.1093/gerona/glq012
  6. Barbat-Artigas S, Rolland Y, Cesari M, Abellan van Kan G, Vellas B, AubertinLeheudre M. Clinical relevance of different muscle strength indexes and functional impairment in women aged 75 years and older. J Gerontol A Biol Sci Med Sci 2013, 68: 811-19. https://doi.org/10.1093/gerona/gls254
  7. Villareal DT, Banks M, Siener C, Sinacore DR, Klein S. Physical frailty and body composition in obese elderly men and women. Obes Res 2004, 12: 913-20. https://doi.org/10.1038/oby.2004.11
  8. Santanasto AJ, Glynn NW, Newman MA, Taylor CA, Brooks MM, Goodpaster BH, Newman AB. Impact of weight loss on physical function with changes in strength, muscle mass, and muscle fat infiltration in overweight to moderately obese older adults: a randomized clinical trial. J Obes 2011, 516576. https://doi.org/10.1155/2011/516576
  9. Verreijen AM, Verlaan S, Engberink MF, Swinkels S, de Vogel-van den Bosch J, Weijs PJ. A high whey protein-, leucine-, and vitamin D-enriched supplement preserves muscle mass during intentional weight loss in obese older adults: a double-blind randomized controlled trial. Am J Clin Nutr 2015, 101: 279-86. https://doi.org/10.3945/ajcn.114.090290
  10. Villareal DT, Chode S, Parimi N, Sinacore DR, Hilton T, Armamento-Villareal R, Napoli N, Qualls C, Shah K. Weight loss, exercise, or both and physical function in obese older adults. New Engl J Med 2011, 364: 1218-29. https://doi.org/10.1056/NEJMoa1008234
  11. Backx EM, Tieland M, Borgonjen-van den Berg KJ, Claessen PR, van Loon LJ, de Groot LC. Protein intake and lean body mass preservation during energy intake restriction in overweight older adults. Int J Obes (Lond) 2016, 40: 299-304. https://doi.org/10.1038/ijo.2015.182
  12. Nicklas BJ, Chmelo E, Delbono O, Carr JJ, Lyles MF, Marsh AP. Effects of resistance training with and without caloric restriction on physical function and mobility in overweight and obese older adults: a randomized controlled trial. Am J Clin Nutr 2015, 101: 991-99. https://doi.org/10.3945/ajcn.114.105270
  13. Porter Starr KN, Pieper CF, Orenduff MC, McDonald SR, McClure LB, Zhou R, Payne ME, Bales CW. Improved function with enhanced protein intake per meal: a pilot study of weight reduction in frail, obese older adults. J Gerontol A Biol Sci Med Sci 2016, 71: 1369-75. https://doi.org/10.1093/gerona/glv210
  14. Steele T, Cuthbertson DJ, Wilding JP. Impact of bariatric surgery on physical functioning in obese adults. Obes Rev 2015, 16: 248-58. https://doi.org/10.1111/obr.12247
  15. Beavers KM, Miller ME, Rejeski WJ, Nicklas BJ, Kritchevsky SB. Fat mass loss predicts gain in physical function with intentional weight loss in older adults. J Gerontol A Biol Sci Med Sci 2013, 68: 80-86. https://doi.org/10.1093/gerona/gls092
  16. Bi X, Loo YT, Henry CJ. Android fat as a determinant of metabolic syndrome: Sex differences. Nutrition 2018, 57: 127-32. https://doi.org/10.1016/j.nut.2018.05.016
  17. Heilbronn LK, Smith SR, Martin CK, Anton SD, Ravussin E. Alternate-day fasting in nonobese participants: effects on body weight, body composition, and energy metabolism. Am J Clin Nutr 2005, 81: 69-73. https://doi.org/10.1093/ajcn/81.1.69
  18. Chomentowski P, Dubé JJ, Amati F, Stefanovic-Racic M, Zhu S, Toledo FGS, Goodpaster BH. Moderate exercise attenuates the loss of skeletal muscle mass that occurs with intentional caloric restriction induced weight loss in older, overweight to obese adults. J Gerontol A Biol Sci Med Sci 2009, 64A: 575-80. https://doi.org/10.1093/gerona/glp007
  19. Miller CT, Fraser SF, Selig SE, Rice T, Grima M, van den Hoek DJ, Ika Sari C, Lambert GW, Dixon JB. Fitness, strength and body composition during weight loss in women with clinically severe obesity: a randomised clinical trial. Obes Facts 2020, 307-21. https://doi.org/10.1159/000506643
  20. Das SK, Roberts SB, Bhapkar MV, Villareal DT, Fontana L, Martin CK, Racette SB, Fuss PJ, Kraus WE, Wong WW, Saltzman E, Pieper CF, Fielding RA, Schwartz AV, Ravussin E, Redman LM for the CALERIE-2 Study Group. Bodycomposition changes in the comprehensive assessment of long-term effects of reducing intake of energy (CALERIE)-2 study: a 2-y randomized controlled trial of calorie restriction in nonobese humans. Am J Clin Nutr 2017, 105: 913-27. https://doi.org/10.3945/ajcn.116.137232
  21. Oh M, Kim S, An KY, Min J, Yang HI, Lee J, Lee MK, Kim DI, Lee HS, Lee JW, KIM DI, Lee HS, Lee JW, Jeon JY. Effects of alternate day calorie restriction and exercise on cardio-metabolic risk factors in overweight and obese adults: An exploratory randomized controlled study. BMC Public Health 2018, 18: 1124. https://doi.org/10.1186/s12889-018-6009-1
  22. Varady KA, Bhutani S, Klempel MC, Kroeger CM, Trepanowski JF, Haus JM, Hoddy KK, Calvo Y. Alternate day fasting for weight loss in normal weight and overweight participants: a randomized controlled trial. Nutr J 2013, 12: 136. https://doi.org/10.1017/S0007114515005346
  23. Bhutani S, Klempel MC, KroegerCM, Trepanowski JF, Varady KA. Alternate day fasting and endurance exercise combine to reduce body weight and favorably alter plasma lipids in obese humans. Obesity 2013, 21: 1370-79. https://doi.org/10.1002/oby.20353
  24. Ho SS, Dhaliwal SS, Hills AP, Pal S. The effect of 12 weeks of aerobic, resistance or combination exercise training on cardiovascular risk factors in the overweight and obese in a randomized trial. BMC Public Health 2012, 12: 704. https://doi.org/10.1186/1471-2458-12-704
  25. Mohammadi HR, Khoshnam MS, Khoshnam E. Effects of different modes of exercise training on body composition and risk factors for cardiovascular disease in middle-aged men. Int J Prev Med 2018, 9: 9. https://doi.org/10.4103/ijpvm.IJPVM_209_16
  26. Tinsley GM, Forsse JS, Butler NK, Paoli A, Bane AA, La Bounty PM, Morgan GB, Grandjean PW. Time-restricted feeding in young men performing resistance training: A randomized controlled trial. Eur J Sport Sci 2017, 17: 200-207. https://doi.org/10.1080/17461391.2016.1223173
  27. Hallsworth K, Fattakhova G, Hollingsworth KG, Thoma C, Moore S, Taylor R, Day CP, Trenell MI. Resistance exercise reduces liver fat and its mediators in non-alcoholic fatty liver disease independent of weight loss. Gut 2011, 60: 1278-83. https://doi.org/10.1136/gut.2011.242073
  28. Ramírez-Vélez R, Izquierdo M, Castro-Astudillo K, Medrano-Mena C, MonroyDíaz AL, del Pilar Castellanos-Vega R, Triana-Reina HR, Correa-Rodríguez María. Weight loss after 12 weeks of exercise and/or nutritional guidance is not obligatory for induced changes in local fat/lean mass indexes in adults with excess of adiposity. Nutrients 2020, 12: 2231. https://doi.org/10.3390/nu12082231
  29. delli Paoli G, van de Laarschot D, Friesema ECH, Verkaik R, Giacco A, Senese R, Arp PP, Jhamai PM, Pagnotta SM, Broer L, Uitterlinden AG, Lanni A, Zillikens MC, de Lange P. Short-term, combined fasting and exercise improves body composition in healthy males. Int J Sport Nutr Exerc Metab 2020, 30: 386-95. https://doi.org/10.1123/ijsnem.2020-0058
  30. Stratton MT, Tinsley GM, Alesi MG, Hester GM, Olmos AA, Serafini P, Modjeski AS, Mangine GT, King K, Savage SN, Webb AT, VanDusseldorp TA. Four weeks of time-restricted feeding combined with resistance training does not differentially influence measures of body composition, muscle performance, resting energy expenditure, and blood biomarkers. Nutrients 2020, 12: 1126. https://doi.org/10.3390/nu12041126
  31. Moro T, Tinsley G, Bianco A, Marcolin G, Francesco Pacelli Q, Battaglia G, Palma A, Gentil P, Neri M, Paoli A. Effects of eight weeks of time-restricted feeding (16/8) on basal metabolism, maximal strength, body composition, inflammation, and cardiovascular risk factors in resistance-trained males. J Transl Med 2016, 14: 290. https://doi.org/10.1186/s12967-016-1044-0
  32. Tinsley GM, Moore ML, Graybeal AJ, Paoli A, Kim Y, Gonzales JU, Harry JR, Van Dusseldorp TA, Kennedy DN, Cruz MR. Time-restricted feeding plus resistance training in active females: a randomized trial. Am J Clin Nutr 2019, 110: 628-40. https://doi.org/10.1093/ajcn/nqz126
  33. Millward DJ, Truby H, Fox KR, Livingstone MB, Macdonald IA, Tothill P. Sex differences in the composition of weight gain and loss in overweight and obese adults. Br J Nutr 2014, 111: 933-43. https://doi.org/10.1017/S0007114513003103
  34. Ryan AS, Harduarsingh-Permaul AS. Effects of weight loss and exercise on trunk muscle composition in older women. Clin Interv Aging 2014, 9: 395-402. https://doi.org/10.2147/CIA.S56662
  35. Teichtahl AJ, Wluka AE,Wang Y, Wijethilake PN, Strauss B, Proietto J, Dixon JB, Jones G, Forbes A, Cicuttini FM. Associations of surgical and nonsurgical weight loss with knee musculature: a cohort study of obese adults. Surg Obes Relat Dis 2016, 12: 158-64.https://doi.org/10.1016/j.soard.2015.04.021
  36. Nylén C, Lundell LS, Massart J, Zierath JR, Näslund E. Short-term low-calorie diet remodels skeletal muscle lipid profile and metabolic gene expression in obese adults. Am J Physiol Endocrinol Metab 2019, 316: E178-85. https://doi.org/10.1152/ajpendo.00253.2018
  37. Egan B, Zierath JR. Exercise metabolism and the molecular regulation of skeletal muscle adaptation. Cell Metab 2013, 17: 162-84. https://doi.org/10.1016/j.cmet.2012.12.012
  38. Weiss EP, Racette SB, Villareal DT, Fontana L, Steger-May K, Schechtman KB, Klein S, Ehsani AA, Holloszy JO. Lower extremity muscle size and strength and aerobic capacity decrease with caloric restriction but not with exerciseinduced weight loss. J Appl Physiol 2007, 102: 634-40. https://doi.org/10.1152/japplphysiol.00853.2006
  39. Ross R, Dagnone D, Jones PJ, Smith H, Paddags A, Hudson R, Janssen I. Reduction in obesity and related comorbid conditions after diet-induced weight loss or exercise-induced weight loss in men: a randomized, controlled trial. Ann Intern Med 2000, 13: 92-103. https://doi.org/10.7326/0003-4819-133-2-200007180-00008
  40. Nissen SL, Sharp RL. Effect of dietary supplements on lean mass and strength gains with resistance exercise: a meta-analysis. J Appl Physiol 2003, 94: 651-59. https://doi.org/10.1152/japplphysiol.00755.2002
  41. Wu H, Xia Y, Jiang J, Du H, Guo X, Liu X, Li C, Huang G, Niu K. Effect of betahydroxy-beta-methylbutyrate supplementation on muscle loss in older adults: a systematic review and meta-analysis. Arch Gerontol Geriatr 2015, 61: 168-75. https://doi.org/10.1016/j.archger.2015.06.020
  42. Campbell WW, Kim JE, Amankwaah AF, Gordon SL, Weinheimer-Haus EM. Higher total protein intake and change in total protein intake affect body composition but not metabolic syndrome indexes in middle-aged overweight and obese adults who perform resistance and aerobic exercisefor 36 weeks. J Nutr 2015, 145: 2076-83. https://doi.org/10.3945/jn.115.213595
  43. Schollenberger AE, Karschin J, Meile T, Kuper MA, Konigsrainer A, Bischoff SC. Impact of protein supplementation after bariatric surgery: a randomized controlled double-blind pilot study. Nutrition 2016, 32: 186-92. https://doi.org/10.1016/j.nut.2015.08.005
  44. Layman DK, Boileau RA, Erickson DJ, Painter JE, Shiue H, Sather C, Christou DD. A reduced ratio of dietary carbohydrate to protein improves body composition and blood lipid profiles during weight loss in adult women. J Nutr 2003, 133: 411-17. https://doi.org/10.1093/jn/133.2.411
  45. Farnsworth E, Luscombe ND, Noakes M, Wittert G, Argyiou E, Clifton PM. Effect of a high-protein, energy-restricted diet on body composition, glycemic control, and lipid concentrations in overweight and obese hyperinsulinemic men and women. Am J Clin Nutr 2003, 78: 31-39. https://doi.org/10.1093/ajcn/78.1.31
  46. Leidy HJ, Carnell NS, Mattes RD, Campbell WW. Higher protein intake preserves lean mass and satiety with weight loss in pre-obese and obese women. Obesity (Silver Spring) 2007, 15: 421-29. https://doi.org/10.1038/oby.2007.531
  47. Meckling KA, Sherfey R. A randomized trial of a hypocaloric high protein diet, with and without exercise, on weight loss, fitness, and markers of the metabolic syndrome in overweight and obese women. Appl Physiol Nutr Metab 2007, 32: 743-52. https://doi.org/10.1139/H07-059
  48. Brehm BJ, D’ Alessio DA. Benefits of high-protein weight loss diets: enough evidence for practice? Curr Opin Endocrinol Diabetes Obes 2008, 15: 416-21. https://doi.org/10.1097/MED.0b013e328308dc13
  49. Smith GI, Julliand S, Reeds DN, Sinacore DR, Klein S, Mittendorfer B. Fish oilderived n3 polyunsaturated fatty acid therapy increases muscle mass and strength in older adults: a randomized controlled trial. Am J Clin Nutr 2015, 102: 115-122, 132. https://doi.org/10.3945/ajcn.114.105833
  50. Longland TM, Oikawa SY, Mitchell CJ, Devries MC, Phillips SM. Higher compared with lower dietary protein during an energy deficit combined with intense exercise promotes greater lean mass gain and fat mass loss: a randomized trial. Am J Clin Nutr 2016, 103: 738-46. https://doi.org/10.3945/ajcn.115.119339
  51. Arciero PJ, Edmonds R, He F, Ward E, Gumpricht E, Mohr A, Ormsbee MJ, Astrup A. Protein-pacing caloric-restriction enhances body composition similarly in obese men and women during weight loss and sustains efficacy during long-term weight maintenance. Nutrients 2016, 8: E476. https://doi.org/10.3390/nu8080476
  52. Moore DR, Robinson MJ, Fry JL, Tang JE, Glover EI, Wilkinson SB, Prior T, Tarnopolsky MA, Phillips SM. Ingested protein dose response of muscle and albumin protein synthesis after resistance exercise in young men. Am J Clin Nutr 2009, 89: 161-68. https://doi.org/10.3945/ajcn.2008.26401
  53. Bohé J, Low A, Wolfe RR, Rennie MJ. Human muscle protein synthesis is modulated by extracellular, not intramuscular amino acid availability: a doseresponse study. J Physiol 2003, 552: 315-24. https://doi.org/10.1113/jphysiol.2003.050674
  54. Rodacki CL, Rodacki AL, Pereira G, Naliwaiko K, Coelho I, Pequito D, Fernandes LC. Fish-oil supplementation enhances the effects of strength training in elderly women. Am J Clin Nutr 2012, 95: 428-36. https://doi.org/10.3945/ajcn.111.021915
  55. Smith GI, Yoshino J, Kelly SC, Reeds DN, Okunade A, Patterson B, Klein S, Mittendorfer B. High protein intake during weight loss therapy eliminates the weight loss-induced improvement in insulin action in postmenopausal women. Cell Reports 2016, 17: 849-61. https://doi.org/10.1016/j.celrep.2016.09.047
  56. Jaspers RT, Zillikens MC, Friesema EC, delli Paoli G, Bloch W, Uitterlinden AG, Goglia F, Lanni A, de Lange P. Exercise, fasting, and mimetics: toward beneficial combinations? FASEB J 2017, 31: 14-28. https://doi.org/10.1096/fj.201600652R
  57. Wang X, Patterson BW, Smith GI, Kampelman J, Reeds DN, Sullivan SA, Mittendorfer BA. 60-min brisk walk increases insulin stimulated glucose disposal but has no effect on hepatic and adipose tissue insulin sensitivity in older women. J Appl Physiol 2013, 114: 1563-68. https://doi.org/10.1152/japplphysiol.01364.2012
  58. Holloszy JO. Exercise-induced increase in muscle insulin sensitivity. J Appl Physiol 2005, 99: 338-43. https://doi.org/10.1152/japplphysiol.00123.2005
  59. Greenhaff PL, Karagounis LG, Peirce N, Simpson EJ, Hazell M, Layfield R, Wackerhage H, Smith K, Atherton P, Selby A. Disassociation between the effects of amino acids and insulin on signaling, ubiquitin ligases, and protein turnover in human muscle. Am J Physiol Endocrinol Metab 2008, 295: E595-604. https://doi.org/10.1152/ajpendo.90411.2008
  60. Louard RJ, Fryburg DA, Gelfand RA, Barrett EJ. Insulin sensitivity of protein and glucose metabolism in human forearm skeletal muscle. J Clin Invest 1992, 90: 348-54. https://doi.org/10.1172/JCI116124
  61. Kim HS, Abbasi F, Lamendola C, McLaughlin T, Reaven GM. Effect of insulin resistance on postprandial elevations of remnant lipoprotein concentrations in postmenopausal women. Am J Clin Nutr 2001, 74: 592-95. https://doi.org/10.1093/ajcn/74.5.592
  62. Reaven GM. Effect of variations in carbohydrate intake on plasma glucose, insulin, and triglyceride responses in normal participants and patients with chemical diabetes. Adv Exp Med Biol 1979, 119: 253-62.
    https://doi.org/10.1007/978-1-4615-9110-8_37
  63. Giacco A, Delli Paoli G, Simiele R, Caterino M, Ruoppolo M, Bloch W, Kraaij R, Uitterlinden AG, Santillo A, Senese R, Cioffi F, Silvestri E, Iervolino S, Lombardi A, Moreno M, Goglia F, Lanni A, de Lange P. Exercise with food withdrawal at thermoneutrality impacts fuel use, the microbiome, AMPK phosphorylation, muscle fibers, and thyroid hormone levels in rats. Physiol Rep 2020, 8: e14354. https://doi.org/10.14814/phy2.14354
  64. Marosi K, Moehl K, Navas-Enamorado I, Mitchell SJ, Zhang Y, Lehrmann E, Aon MA, Cortassa S, Becker KG, Mattson MP. Metabolic and molecular framework for the enhancement of endurance by intermittent food deprivation. FASEB J 2018, 32: 3844-58. https://doi.org/10.1096/fj.201701378RR
  65. França GO, Frantz EDC, Magliano DC, Bargut TCL, Sepúlveda-Fragoso V, Silvares RR, Daliry A, Nascimento ARD, Borges JP. Effects of short-term highintensity interval and continuous exercise training on body composition and cardiac function in obese sarcopenic rats. Life Sci 2020, 256: 117920. https://doi.org/10.1016/j.lfs.2020.117920
  66. Lancel S, Hesselink MK, Woldt E, Rouillé Y, Dorchies E, Delhaye S, Duhem C, Thorel Q, Mayeuf-Louchart A, Pourcet B, Montel V, Schaart G, Beton N, Picquet F, Briand O, Salles JP, Duez H, Schrauwen P, Bastide B, Bailleul B, Staels B, Sebti Y. Endospanin-2 enhances skeletal muscle energy metabolism and running endurance capacity. JCI Insight 2018, 3: e98081. https://doi.org/10.1172/jci.insight.98081
  67. Bujak AL, Crane JD, Lally JS, Ford RJ, Kang SJ, Rebalka IA, Green AE, Kemp BE, Hawke TJ, Schertzer JD, Steinberg GR. AMPK activation of muscle autophagy prevents fasting-induced hypoglycemia and myopathy during aging. Cell Metab 2015, 6: 83-90. https://doi.org/10.1016/j.cmet.2015.05.016
  68. Pasiakos SM, Cao JJ, Margolis LM, Sauter ER, Whigham LD, McClung JP, Rood JC, Carbone JW, Combs GF Jr, Young AJ. Effects of high-protein diets on fat-free mass and muscle protein synthesis following weight loss: a randomized controlled trial. FASEB J 2013, 27: 3837-47. https://doi.org/10.1096/fj.13-230227
  69. Hector AJ, Marcotte GR, Churchward-Venne TA, Murphy CH, Breen L, von Allmen M, Baker SK, Phillips SM. Whey protein supplementation preserves postprandial myofibrillar protein synthesis during short-term energy restriction in overweight and obese adults. J Nutr 2015, 145: 246-52. https://doi.org/10.3945/jn.114.200832
  70. Murphy CH, Churchward-Venne TA, Mitchell CJ, Kolar NM, Kassis A, Karagounis LG, Burke LM, Hawley JA, Phillips SM. Hypoenergetic dietinduced reductions in myofibrillar protein synthesis are restored with resistance training and balanced daily protein ingestion in older men. Am J Physiol Endocrinol Metab 2015, 308: E734-43. https://doi.org/10.1152/ajpendo.00550.2014
  71. Campbell WW, Haub MD, Wolfe RR, Ferrando AA, Sullivan DH, Apolzan JW, Iglay HB. Resistance training preserves fat-free mass without impacting changes in protein metabolism after weight loss in older women. Obesity (Silver Spring) 2009, 17: 1332-39. https://doi.org/10.1038/oby.2009.2
  72. Villareal DT, Smith GI, Shah K, Mittendorfer B. Effect of weight loss on the rate of muscle protein synthesis during fasted and fed conditions in obese older adults. Obesity (Silver Spring) 2012, 20: 1780-86. https://doi.org/10.1038/oby.2011.280
  73. Zheng L, Rao Z, Guo Y, Chen P, Xiao W. High-intensity interval training restores glycolipid metabolism and mitochondrial function in skeletal muscle of mice with type 2 diabetes. Front Endocrinol 2020, 11: 561. https://doi.org/10.3389/fendo.2020.00561
  74. Brandt N, Gunnarsson TP, Bangsbo J, Pilegaard H. Exercise and exercise training induced increase in autophagy markers in human skeletal muscle. Physiol Rep 2018, 6: e13651. https://doi.org/10.14814/phy2.13651
  75. Ulbricht A, Gehlert S, Leciejewski B, Schiffer T, Bloch W, Höhfeld J. Induction and adaptation of chaperone-assisted selective autophagy CASA in response to resistance exercise in human skeletal muscle. Autophagy 2015, 11: 538-46. https://doi.org/10.1080/15548627.2015.1017186
  76. Zheng DM, Bian Z, Furuya N, Oliva Trejo JA, Takeda-Ezaki M, Takahashi K, Hiraoka Y, Mineki R, Taka H, Ikeda S, Komatsu M, Fujimura T, Ueno T, Ezaki J. A treadmill exercise reactivates the signaling of the mammalian target of rapamycin (mTor) in the skeletal muscles of starved mice. Biochem Biophys Res Commun 2015, 56: 519-26. https://doi.org/10.1016/j.bbrc.2014.11.118
  77. Dethlefsen MM, Bertholdt L, Gudiksen A, Stankiewicz T, Bangsbo J, van Hall G, Plomgaard P, Pilegaard H. Training state and skeletal muscle autophagy in response to 36 h of fasting. J Appl Physiol 2018, 125: 1609-19. https://doi.org/10.1152/japplphysiol.01146.2017
  78. Møller AB, Vendelbo MH, Christensen B, Clasen BF, Bak AM, Jørgensen JO, Møller N, Jessen N. Physical exercise increases autophagic signaling through ULK1 in human skeletal muscle. J Appl Physiol 2015, 118: 971-79. https://doi.org/10.1152/japplphysiol.01116.2014
  79. Van Proeyen K, De Bock K, Hespel P. Training in the fasted state facilitates re-activation of eEF2 activity during recovery from endurance exercise. Eur J Appl Physiol 2011, 7: 1297-1305. https://doi.org/10.1007/s00421-010-1753-7
  80. De Bock K, Richter EA, Russell AP, Eijnde BO, Derave W, Ramaekers M, Koninckx E, Léger B, Verhaeghe J, Hespel P. Exercise in the fasted state facilitates fibre type-specific intramyocellular lipid breakdown and stimulates glycogen resynthesis in humans. J Physiol 2005, 564: 649-60. https://doi.org/10.1113/jphysiol.2005.083170
  81. Dethlefsen MM, Bertholdt L, Gudiksen A, Stankiewicz T, Bangsbo J, van Hall G, Plomgaard P, Pilegaard H. Training state and skeletal muscle autophagy in response to 36 h of fasting. J Appl Physiol 2018, 125: 1609-19. https://doi.org/10.1152/japplphysiol.01146.2017