Optimising dietary macronutrient intake for cutaneous and burn wound healing using the Geometric Framework

Abstract

Background Nutritional support in the form of macronutrients (protein, carbohydrate and fat) for severe burn injury is an essential component of modern burn care. Current best practice involves the use of high-energy, high-protein diets to aid burn wound healing and to reduce the catabolic sequelae of hypermetabolism. The purpose of this PhD project was to investigate the effect of macronutrients on skin structure, healing of simple cutaneous wounds and finally healing of complex burn wounds in mice using a novel method of analysis known as the Geometric Framework (GF). The overall aim of the study was to identify the most favourable ratio of macronutrients for cutaneous and burn wound healing. Methods For chapters 2, 3 and 5, the GF a recently developed modelling platform that permits analysis of the simultaneous, individual and interactive effects of macronutrients on an organism and its environment was used to investigate the effect of nutrition on skin structure (Chapter 2), cutaneous healing (Chapter 3) and burn wound healing (Chapter 5) in a mouse model. For Chapter 4 a mouse model of post-burn hypermetabolism was developed and characterised using histological, biochemical techniques and metabolic cages. Results Chapter 2: The effect of macronutrients on skin structure:The effects of long-term macronutrient intake on skin structure are sex specific, with high-protein intake increasing male dermis thickness. Skin changes in female mice were less noticeable and primarily driven by carbohydrate intake. Dermal thickness and subcutaneous fat thickness were found to be inversely proportional in both sexes. Chapter 3: The effect of macronutrients on cutaneous wound healing:Cutaneous wound healing was found to be optomised by a low-protein intake (5% total energy intake) with equal intake of carbohydrate and fat (48% carbohydrate and fat). Mice fed this diet had favourable wound cytokine expression, faster epidermal migration and cell proliferation and improved collagen deposition. Systemically, accelerated healing was associated with a greater systemic inflammatory response, loss of lean body mass, higher energy expenditure, increased weight and expression of uncoupling protein-1 in inguinal white fat and brown adipose tissue. Chapter 4: Development and characterisation of a mouse model of hypermetabolism:Large burn injury when compared to small burn injury resulted in a profound and prolonged period of hypermetabolism, with a significantly increased basal energy expenditure and loss of lean mass. The model was further characterised to show that a large burn injury in mice is capable of mimicking many aspects of human burn injury pathophysiology including cytokines, hormonal and organ abnormalities. Chapter 5: The effect of macronutrients on burn injury healing and hypermetabolism:Wound healing in a hypermetabolic mouse model was accelerated by a moderate-protein, high-carbohydrate, low-fat intake at a ratio of protein:carbohydrate:fat of 1:4:2. High protein intake was essential early after burn injury to prevent mortality and weight-loss, but was associated with delayed wound healing in later stages. Conclusions Cutaneous healing in mice is accelerated by a low-protein intake and burn wound healing is accelerated by a moderate-protein intake. After burn injury, a high-carbohydrate intake was beneficial, especially when compared to the effects of a high-fat intake. This research has the potential to alter practice in global wound management by challenging the current use of high-protein diets for cutaneous and burn wounds and confirms the benefits of a high-carbohydrate rather than a high-fat intake for improving outcomes after burn injury.