Biological control of appetite: A daunting complexity

Abstract

Objective: This review summarizes a portion of the discussions of an NIH Workshop (Bethesda, MD, 2015) titled "Self-Regulation of Appetite-It's Complicated," which focused on the biological aspects of appetite regulation.

Methods: This review summarizes the key biological inputs of appetite regulation and their implications for body weight regulation.

Results: These discussions offer an update of the long-held, rigid perspective of an "adipocentric" biological control, taking a broader view that also includes important inputs from the digestive tract, from lean mass, and from the chemical sensory systems underlying taste and smell. It is only beginning to be understood how these biological systems are integrated and how this integrated input influences appetite and food eating behaviors. The relevance of these biological inputs was discussed primarily in the context of obesity and the problem of weight regain, touching on topics related to the biological predisposition for obesity and the impact that obesity treatments (dieting, exercise, bariatric surgery, etc.) might have on appetite and weight loss maintenance. Finally considered is a common theme that pervaded the workshop discussions, which was individual variability.

Conclusions: It is this individual variability in the predisposition for obesity and in the biological response to weight loss that makes the biological component of appetite regulation so complicated. When this individual biological variability is placed in the context of the diverse environmental and behavioral pressures that also influence food eating behaviors, it is easy to appreciate the daunting complexities that arise with the self-regulation of appetite.

Figure 1. Biological Inputs of Appetite Regulation

The key biological affectors of appetite are placed in the context of the energy balance relationship (energy intake, EI; expended energy, EE; thermic effect of food, TEF; exercise activity thermogenesis, EAT; resting energy expenditure, REE; resting metabolic rate, RMR)). Separate effects of fat-free mass (FFM) and fat mass (FM) denote stimulatory and inhibitory inputs, respectively. The gut provides feedback through neural and endocrine paths that involve the episodic hunger and satiety signals coincident to nutrient availability and the prandial state. These biological inputs operate in a neural architecture established early in life that dictates food preferences. Exercise may influence appetite through its impact on these biological inputs, but its overall impact is variable and complicated by compensatory food eating behaviors. The built-in redundancies, complexities, and individual variability, with each aspect of food preference and these feedback systems, which are rooted in the underlying genetics, establish a daunting biological complexity to the nature of appetite control.

Figure 2. Relationship between RMR and Self-Determined Intake

Scatter plot and standardized β-coefficient to illustrate the relationship between resting metabolic rate RMR and daily energy intake in 59 individuals. While the underlying mechanisms remain elusive, this is one of many studies showing a strong association between fat free mass, the metabolic requirements of the body, and the drive to eat.

Figure 3. Individual Variability in the Response to Supervised Exercise

Data taken from the studies of King et al (90, 97) showing the wide variation in body weights and body fat in a group of overweight and obese individuals who completed 12 weeks of supervised and measured physical activity (5 sessions per week) designed to expend 2 MJ per session. These studies revealed that the effect of exercise on appetite regulation involves at least 2 processes: an increase in the overall (orexigenic) drive to eat and a concomitant increase in the satiating efficiency of a fixed meal. The individual variability in the overall response is likely rooted, at least in part, in how exercise differentially affects these two processes between individuals.