Low-protein diet accelerates wound healing in mice post-acute injury

Jonathan J. Hew; Roxanne J. Parungao; Craig P. Mooney; Julian K. Smyth; Sarah Kim; Kevin H.-Y. Tsai; Huaikai Shi; Cassandra Chong; Renee C. F. Chan; Beba Attia; Caroline Nicholls; Zhe Li; Samantha M. Solon-Biet; David G. Le Couteur; Stephen J. Simpson; Marc G. Jeschke; Peter K. Maitz; Yiwei Wang

doi:10.1093/burnst/tkab010

Burns & Trauma ›› 2021, Vol. 9 ›› Issue (1) :tkab010 DOI: 10.1093/burnst/tkab010

Research Article

research-article

Low-protein diet accelerates wound healing in mice post-acute injury

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¹ Burns Research and Reconstructive Surgery, ANZAC Research Institute, Concord Hospital, University of Sydney , Sydney, Australia 2139

² Bone Biology Group, ANZAC Research Institute, Concord Hospital, University of Sydney , Sydney, Australia 2139

³ Adrenal Steroids Laboratory, ANZAC Research Institute, Concord Hospital, University of Sydney , Sydney, Australia 2139

⁴ Electron Microscopy Unit, Anatomical Pathology, Concord Hospital , Sydney, Australia 2139

⁵ Burns Unit, Concord Repatriation General Hospital , Concord, Australia 2139

⁶ Ageing and Alzheimer Institute and ANZAC Research Institute, Concord Hospital, University of Sydney , Sydney, Australia 2139

⁷ Charles Perkins Centre and School of Life and Environmental Sciences, University of Sydney , Australia 2006

⁸ Sunnybrook Research Institute , Toronto, Ontario, Canada, M4N 3M5

⁹ School of Pharmacy, Nanjing University of Chinese Medicine , Nanjing, PR China 210023

^*Email: yiweiwang@anzac.edu.au,yiweiwang@njucm.edu.cn

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Abstract

Background: Wound healing processes are influenced by macronutrient intake (protein, carbohydrate and fat). The most favourable diet for cutaneous wound healing is not known, although high-protein diets are currently favoured clinically. This experimental study investigates the optimal macronutrient balance for cutaneous wound healing using a mouse model and the Geometric Framework, a nutrient modelling method, capable of analyzing the individual and interactive effects of a wide spectrum of macronutrient intake. Methods: Two adjacent and identical full-thickness skin excisions (1 cm²) were surgically created on the dorsal area of male C57BL/6 mice. Mice were then allocated to one of 12 high-energy diets that varied in protein, carbohydrate and fat content. In select diets, wound healing processes, cytokine expression, energy expenditure, body composition, muscle and fat reserves were assessed. Results: Using the Geometric Framework, we show that a low-protein intake, coupled with a balanced intake of carbohydrate and fat is optimal for wound healing. Mice fed a low-protein diet progressed quickly through wound healing stages with favourable wound inflammatory cytokine expression and significantly accelerated collagen production. These local processes were associated with an increased early systemic inflammatory response and a higher overall energy expenditure, related to metabolic changes occurring in key macronutrient reserves in lean body mass and fat depots. Conclusions: The results suggest that a low-protein diet may have a greater potential to accelerate wound healing than the current clinically used high-protein diets.

Keywords

Wound healing / Macronutrients / Cutaneous / Geometric Framework / Mouse model / Low-protein diet / Nutrition

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Jonathan J. Hew, Roxanne J. Parungao, Craig P. Mooney, Julian K. Smyth, Sarah Kim, Kevin H.-Y. Tsai, Huaikai Shi, Cassandra Chong, Renee C. F. Chan, Beba Attia, Caroline Nicholls, Zhe Li, Samantha M. Solon-Biet, David G. Le Couteur, Stephen J. Simpson, Marc G. Jeschke, Peter K. Maitz, Yiwei Wang. Low-protein diet accelerates wound healing in mice post-acute injury. Burns & Trauma, 2021, 9 (1) : tkab010 DOI:10.1093/burnst/tkab010

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References

Publishing order | Descend order by publishing year | Descend order by cited within

[1]	Brown KL, Phillips TJ. Nutrition and wound healing. Clin Dermatol. 2010; 28: 432-9.

[2]	Wild T, Rahbarnia A, Kellner M, Sobotka L, Eberlein T. Basics in nutrition and wound healing. Nutrition. 2010; 26: 862-6.

[3]	Dylewski ML, Yu YM. Protein and wound healing. In: Molnar JA (ed). Nutrition and Wound Healing. Florida: CRC press, 2007, 49-65.

[4]	Calder CP, Dimitriadis CG, Newsholme CP. Glucose metabolism in lymphoid and inflammatory cells and tissues. Curr Opin Clin Nutr Metab Care. 2007; 10: 531-40.

[5]	Turek JJ.Fat and wound healing. In: Molnar JA (ed). Nutrition and wound healing. Florida: CRC press, 2007, 27-48.

[6]	Demling RH. Nutrition, anabolism, and the wound healing process: an overview. Eplasty. 2009; 9: 65-94.

[7]	Stechmiller JK. Understanding the role of nutrition and wound healing. Nutr Clin Pract. 2010; 25: 61-8.

[8]	Weimann A, Braga M, Carli F, Higashiguchi T, Hubner M, Klek S, et al. ESPEN guideline: clinical nutrition in surgery. Clin Nutr. 2017; 36: 623-50.

[9]	Yoshino Y, Ohtsuka M, Kawaguchi M, Sakai K, Hashimoto A, Hayashi M, et al. The wound/burn guidelines-6: guidelines for the management of burns. J Dermatol. 2016; 43: 989-1010.

[10]	Simpson SJ, Raubenheimer D. The Nature of Nutrition: A Unifiying Framework from Animal Adaptation to Human Obesity. Princeton: Princeton University Press, 2012.

[11]	Masters B, Arabi S, Sidhwa F, Wood F. High-carbohydrate, high-protein, low-fat versus low-carbohydrate, high-protein, high-fat ente1ral feeds for burns (review). Cochrane Collaboration. 2012; 2: 1-21.

[12]	Weir JBV.New method for calculating metabolic reate with special reference to protein metabolism. J Biochem Physiol. 1949; 109: 1-9.

[13]	Derde S, Vanhorebeek I, Guiza F, Derese I, Gunst J, Fahrenkrog B, et al. Early parenteral nutrition evokes a phenotype of autophagy deficiency in liver and skeletal muscle of critically ill rabbits. Endocrinology. 2012; 153: 2267-76.

[14]	Bodine SC, Baehr LM. Skeletal muscle atrophy and the E3 ubiquitin ligases MuRF1 and MAFbx/atrogin-1. Am J Physiol Endocrinol Metab. 2014; 307: E469-84.

[15]	Mizushima N, Yoshimori T, Levine B. Methods in mammalian autophagy research. Cell. 2010; 140: 313-26.

[16]	Lin Z-Q, Kondo T, Ishida Y, Takayasu T, Mukaida N. Essential involvement of IL-6 in the skin wound-healing process as evidenced by delayed wound healing in IL-6-deficient mice. J Leukoc Biol. 2003; 73: 713-21.

[17]	Gharaee-Kermani M, Phan SH. Role of cytokines and cytokine therapy in wound healing and fibrotic diseases. Curr Pharm Des. 2001; 7: 1083-103.

[18]	Alves CC, Torrinhas RS, Giorgi R, Brentani MM, Logullo AF, Waitzbery DL. TGF-β1 expression in wound healing is acutely affected by experimental malnutrition and early enteral feeding. Int Wound J. 2014; 11: 533-9.

[19]	Zamir O, Hasselgren P-O, Higashiguchi T, Frederick JA, Fischer JE. Tumor necrosis factor (TNF) and interleukin-1 (IL-1) induce muscle proteolysis through different mechanisms. Mediators Inflamm. 1992; 1: 247-50.

[20]	Patel JJ, Martindale RG, McClave SA. Controversies surrounding critical care nutrition: an appraisal of permissive underfeeding, protein, and outcomes. JPEN J Parenter Enteral Nutr. 2018; 42: 508-15.

[21]	Pezeshki A, Zapata RC, Singh A, Yee NJ, Chelikani PK. Low protein diets produce divergent effects on energy balance. Sci Rep. 2016; 6: 25145.

[22]	Huang X, Hancock DP, Gosby AK, McMahon AC, Solon SMC, Le Couteur DG, et al. Effects of dietary protein to carbohydrate balance on energy intake, fat storage, and heat production in mice. Obesity. 2013; 21: 85-92.

[23]	Leeds IL, Wick EC, Melton GB. Does close temperature regulation affect surgical site infection rates? Adv Surg. 2014; 48: 65-76.

[24]	Wray CJ, Mammen JMV, Hasselgren P-O. Catabolic response to stress and potential benefits of nutrition support. Nutrition. 2002; 18: 971-7.

[25]	Belghit I, Panserat S, Sadoul B, Dias K, Skiba-Cassy S, Seiliez I. Macronutrient composition of the diet affects the feeding-mediated down regulation of autophagy in muscle of rainbow trout. PLoS One. 2013; 8: 1-14.

[26]	Oczypok EA, Oury TD, Chu CT. It’s a cell-eat-cell world. Am J Pathol. 2013; 182: 612-22.

[27]	Preiser J-C, van Zanten ARH, Berger MM, Biolo G, Casaer MP, Doig GS, et al. Metabolic and nutritional support of critically ill patients: consensus and controversies. Crit Care. 2015; 19: 35.