In this paper, we discuss different ways that energy balance can be achieved and the potential consequences for longer term body weight regulation with special attention to the weight-reduced state. We focus on the concept of energy flux from a theoretical perspective, the components of energy flux, the impact of various modes and intensities of exercise on energy flux, and the potential advantages of achieving post-weight loss energy balance and weight maintenance at higher levels of energy intake and expenditure (high energy flux). This is not meant to be an exhaustive review, but rather to propose that based on evolutionary biology and high food availability in our current environment, high energy flux is inevitable, but how a high energy flux state is re-established following weight loss is critical to long term healthy weight management.

Decades of research have shown that calorie-restricted diets of any macronutrient composition rarely result in permanent weight loss, and that long-term success rates for obesity treatment (apart from bariatric surgery) are low [ 1 ]. In light of this phenomenon, the U.S. National Institutes of Health sponsored a 2019 workshop titled, The Physiology of the Weight-Reduced State, for the purpose of addressing the issue of poor long-term obesity treatment outcomes. Discussions at this workshop centered on the contributions of genetics and the environment to the epidemic of obesity, as well as the physiological adaptations, behaviors/habits and the obesogenic environment interacting to present significant barriers to long-term weight loss. There was general consensus that energy restriction leading to the weight-reduced state is characterized by decreased total daily energy expenditure and increased hunger. Moderators called for greater research efforts focused on creative approaches to overcome these barriers such that energy balance and maintenance of the lost body mass (primarily fat mass) can be achieved in the face of these metabolic adaptations that are at odds with the current obesogenic environment.

2. How is Energy Flux Defined and Measured?

The term ‘flux’ in biology refers to a relatively simple concept—the rate of movement of a substance, such as calcium ions, from one cellular compartment or tissue to another, which takes into account the magnitude and direction of flow (both efflux and influx) of the substance. Germaine to cellular bioenergetics, one can speak of ATP flux as ATP turnover, which involves the dual processes of ATP hydrolysis and synthesis required for biological work. In regard to body weight regulation, a number of different definitions and explanations for the concept of energy flux can be found in the scientific literature and these typically take a macroscopic, whole-body view. Unfortunately, the use of this term is inconsistent and has led to some confusion. Bell et al. [ 2 ] specified energy flux as the “absolute level of energy intake and expenditure under conditions of energy balance”. In a similar fashion, Goran et al. [ 3 ], Bullough et al. [ 4 ], and Hagele et al. [ 5 ] have used the term in experimental studies to describe ‘energy turnover’, occurring as a function of total daily energy intake (TDEI) matched to daily expenditure. Similarly, Swinburn et al. [ 6 ] have used the term to describe total daily energy expenditure (TDEE) based on doubly-labeled water studies with the assumption that during the several weeks of TDEE measurement, individuals were in energy balance and metabolizable energy from food was approximately equal to TDEE. Hume et al. [ 7 ] defined energy flux as habitual energy intake plus habitual energy expenditure and then later in the same paper they described energy flux as the ‘absolute level of energy balance’. In a more mechanistic description, Hand et al. [ 8 ] defined energy flux as “the rate of caloric conversion from initial absorption into the body tissues to utilization in metabolism or its transformation into energy stores”. Their definition, encompassing the process of transforming ingested energy into body energy stores, does not assume energy flux to be characterized by a state of energy balance. It is apparent then, that the use of the term ‘energy flux’ is not uniformly consistent and its relationship with energy balance is not consistently described.

The magnitude of energy turnover in the body during a given time period is dependent on energy expenditure, independent of whether the energy provided is from ingested energy or endogenous stores. While it may be reasonable to define energy flux as TDEE in a steady state where metabolizable energy from food and energy expenditure are matched, it is also important to understand differences in how that energy expenditure is achieved. In other words, simply considering energy flux as total energy expenditure fails to consider the individual contributions of resting energy expenditure (REE), the thermic effect of feeding (TEF), exercise energy expenditure (ExEE), and non-exercise activity thermogenesis (NEAT). The latter two are the components of physical activity energy expenditure (PAEE).

3,4,6,9, While low and high flux conditions have been previously described as energy balanced states with no net loss or gain of energy stores over time [ 2 10 ], one might argue that high and low flux states can occur at least initially, with some degree of energy imbalance. For example, an individual who expends a total of 10,460 kJ/day (2500 kcal/day), but only consumes 8368 kJ/day (2000 kcal) of metabolizable food energy, still has an energy flux of 10,460 kJ/day (at least initially). The energy requirement is readily met by the influx of 8368 kJ/day of metabolizable energy ingested and an additional 2092 kJ/day (500 kcal/day) drawn from the body’s energy stores. Thus, energy flux could be measured at any point in time as energy expenditure regardless of whether the energy comes from exogenous or endogenous sources. However, energy flux as a concept related to the maintenance of lost weight is likely to be more useful in reference to periods of weeks to months. Given that a goal of obesity treatment is maintenance of lost weight in a state of energy balance, when examining the role of energy flux in preventing weight regain, our working definition of energy flux is the magnitude of total energy turnover while maintaining energy balance over periods of weeks to months. Consistency in how the term is used among studies would be helpful in determining the level of importance this concept has for body weight regulation.

Although energy flux is a function of intake (influx) and expenditure (efflux), these should not be summed to quantify flux, as this inflates the actual throughput of energy in the body [ 11 ]. The magnitude of energy flux can be expressed as both absolute and relative values. The former is synonymous with TDEE; the latter is expressed relative to body size or to REE, thus allowing comparisons between individuals with differing body sizes and REE values. One possibility is to express flux as a multiple of REE (TDEE/REE) [ 10 ], which has also been termed metabolic scope [ 12 ]. This approach provides a measure of flux that is synonymous with that of the commonly used physical activity level (PAL) used to describe the range of daily energy expenditures—from those of sedentary individuals to athletes. It is also similar to the concept of metabolic equivalents (METs, multiples of REE) used to quantify physical activity and exercise intensities as fold changes in energy expenditure relative to rest. Thus, an individual with a TDEE of 10,460 kJ/day (2500 kcal/d) and an REE of 6276 kJ/day (1500 kcal/d), would have an absolute energy flux of 10,460 kJ/day and a metabolic scope of 1.67 that represents relative energy flux. Using this approach, it may be possible to identify an optimum energy flux for an individual or a population. A similar approach might be to quantify energy flux as non-REE by subtracting REE from TDEE. However, REE is also the major contributor to TDEE (except for athletes who on some days are training extensively and exhibit extremely high levels of PAEE). So, a person with a high REE (as in the case of obesity) could have the same absolute energy flux as a smaller, highly physically active person with a much lower REE, but the contributors to high energy flux would be quite different and these metabolic states are also quite different.

While acknowledging the inherent difficulties in arriving at a standard approach to measuring energy flux, we propose that energy flux should be quantified in both absolute (TDEE while in energy balance) and relative terms as metabolic scope (TDEE/REE while in energy balance). Quantifying absolute energy flux as TDEE demonstrates that similar levels of high flux are achievable by sedentary persons with large body mass and by physically active persons with much lower body mass. Quantifying relative energy flux demonstrates the different contributions of non-REE (primarily PAEE) to the magnitude of energy flux in these two individuals. This use of the metabolic scope as a relative measure of flux is an especially useful construct in regard to the weight-reduced state, as it focuses on the importance of increasing TDEE not by weight regain and associated increases in REE, but by increasing the contribution of PAEE to TDEE independent of increases in body mass. Furthermore, for reasons discussed later in our concept paper, we propose that in the weight-reduced state, achieving a metabolic scope of 1.7–1.8 would be a starting point for a “desired value”, although much more investigative work is required in this important research area.