Novel dietary approaches to appetite regulation, health and performance

Abstract

Nutrition and metabolism are fundamental to understanding the physiological basis of the most prevalent diseases currently in society. Cardiovascular disease, type 2 diabetes and even dementia have a metabolic underpinning (Reaven, 1988; Ferrari & Sorbi, 2021). Diet-related chronic diseases account for at least 9% of the National Health Service budget in the UK; which equates to at least £12 billion per annum (DEFRA, 2014). In addition to health, nutrition is fundamental to optimizing human performance via the provision of chemical energy in addition to modulating adaptation to exercise (Burke & Hawley, 2018). Therefore, understanding the physiology of nutrition can aid in reducing disease burden and extending the limits of human performance. ‘Novel dietary approaches to appetite regulation, health and performance’ was the title of a Highlighted Symposium originally due to be delivered in 2020, but delayed by a year and delivered online as part of the 2021 American College of Sports Medicine Annual meeting, and was supported by The Journal of Physiology. The aim of this symposium was for the four speakers to cover new ways in which nutrition can be used to regulate appetite and improve human health and performance. An emerging theme was the role of nutrient timing, possibly reflecting the increasing focus on when we eat in addition to what we eat. Smith and Betts (2022) provide an overarching review of how circadian rhythms relate to nutrition, physical activity and light exposure. Metabolic responses to food ingestion are dependent on the time of day. Glucose and triacylglycerol concentrations, for example, typically show larger postprandial increases in the evening versus the morning (Smith & Betts, 2022). These responses are likely mediated by diurnal rhythms in β-cell function, insulin secretion, clearance and sensitivity, very low density lipoprotein secretion and intestinal triacylglycerol absorption (Smith & Betts, 2022). With respect to appetite regulation, hunger ratings during constant routine and forced desynchrony protocols are commonly reported to be lowest in the morning and peak in the evening, which may partly be regulated by variation in gut peptide concentrations (Templeman et al. 2021b). Given that nutrition is a key signal for biological rhythms, the role of manipulating nutrient timing on physiological responses was discussed. Whilst continuous 24 h feeding appears to disrupt some aspects of hormonal regulation (Gonzalez et al. 2020), extending the overnight fast (i.e. skipping breakfast), can increase the glycaemic responses to lunch (the contrasting response to breakfast consumption is commonly referred to as the second-meal effect) (Gonzalez et al. 2013). When breakfast skipping is extended over 6 weeks, there is evidence of more stable interstitial glucose concentrations and altered mRNA expression in adipose tissue (Betts et al. 2014; Gonzalez et al. 2018). Extending fasting periods to 24 h with a form of intermittent fasting known as alternate day fasting, can be a useful strategy to achieve an energy deficit, but in many paradigms it is difficult to disentangle the effects of fasting from a negative energy balance. When the degree of energy deficit is matched, there is emerging evidence that alternate day fasting (24 h of fasting followed by 24 h of feeding), does not substantially alter metabolic responses but may result in lower physical activity energy expenditure and a greater proportion of weight loss from fat-free mass rather than fat mass (Templeman et al. 2021a); possibly due to extended periods of exogenous amino acid restriction combined with lower physical activity. Gabel and Varady (2022) discuss the evidence on another variation of intermittent fasting known as time-restricted eating, with respect to body mass and cardiometabolic health. Time-restricted eating refers to a confined eating window within each day, normally between 4 and 10 h, and fasting for the remaining time of each 24 h period. The variations that can therefore exist within this protocol include the duration and timing of the eating window, and the macronutrient composition of the diet. In a similar fashion to alternate day fasting, the responses to these diets can be understood within the context of allowing total energy intake to vary naturally, or to specifically match comparator diets isoenergetically (i.e. to understand the effects of time-restricted eating independent of any differences in energy balance). Whilst there is promising emerging evidence that time-restricted eating can produce weight loss via a spontaneous energy deficit, there are potential concerns over loss of fat-free mass (Lowe et al. 2020), and the evidence is more equivocal on markers of metabolic health such as fasting plasma glucose concentrations, low density lipoprotein-cholesterol and triacylglycerol concentrations (Gabel & Varady, 2022). There is also a current lack of long-term (>12 weeks) data to understand the chronic responses to time-restricted eating. Edinburgh et al. (2022) review the responses to extended overnight fasting within the context of prescribed exercise. Evidence is developing to indicate that performing exercise with lower carbohydrate and/or higher fatty acid availability may enhance some adaptations to exercise training. One of the primary metabolic adaptations to regular exercise training is an increase in insulin sensitivity, and major mechanisms contributing to this adaptation include molecular changes in skeletal muscle (Edinburgh et al. 2022). With each bout of exercise, a number of pathways in skeletal muscle are activated (e.g. AMP-activated protein kinase, Akt substrate of 160 kDa, Rac1 and Ca2+/calmodulin-dependent protein kinase II), leading to acute improvements in insulin sensitivity via increases in the translocation of GLUT4 to the skeletal muscle plasma membrane, and increases in microvascular perfusion. Over longer time frames, regular exercise results in an increase in skeletal muscle GLUT4 protein content, mitochondrial content and function. Nutrition appears to modulate some of these adaptations to acute and