The idea of body weight regulation implies that a biological mechanism exerts control over energy expenditure and food intake. This is a central tenet of energy homeostasis. However, the source and identity of the controlling mechanism have not been identified, although it is often presumed to be some long-acting signal related to body fat, such as leptin. Using a comprehensive experimental platform, we have investigated the relationship between biological and behavioural variables in two separate studies over a 12-week intervention period in obese adults (totaln92). All variables have been measured objectively and with a similar degree of scientific control and precision, including anthropometric factors, body composition, RMR and accumulative energy consumed at individual meals across the whole day. Results showed that meal size and daily energy intake (EI) were significantly correlated with fat-free mass (FFM,Pvalues < 0·02–0·05) but not with fat mass (FM) or BMI (Pvalues 0·11–0·45) (study 1,n58). In study 2 (n34), FFM (but not FM or BMI) predicted meal size and daily EI under two distinct dietary conditions (high-fat and low-fat). These data appear to indicate that, under these circumstances, some signal associated with lean mass (but not FM) exerts a determining effect over self-selected food consumption. This signal may be postulated to interact with a separate class of signals generated by FM. This finding may have implications for investigations of the molecular control of food intake and body weight and for the management of obesity.

Energy balance is not a simple algebraic sum of energy expenditure and energy intake as often depicted in communications. Energy balance is a dynamic process and there exist reciprocal effects between food intake and energy expenditure. An important distinction is that of metabolic and behavioural components of energy expenditure. These components not only contribute to the energy budget directly, but also by influencing the energy intake side of the equation. It has recently been demonstrated that resting metabolic rate (RMR) is a potential driver of energy intake, and evidence is accumulating on the influence of physical activity (behavioural energy expenditure) on mechanisms of satiety and appetite control. These effects are associated with changes in leptin and insulin sensitivity, and in the plasma levels of gastrointestinal (GI) peptides such as glucagon-like peptide-1 (GLP-1), ghrelin and cholecystokinin (CCK). The influence of fat-free mass on energy expenditure and as a driver of energy intake directs attention to molecules emanating from skeletal tissue as potential appetite signals. Sedentariness (physical inactivity) is positively associated with adiposity and is proposed to be a source of overconsumption and appetite dysregulation. The molecular signals underlying these effects are not known but represent a target for research.

Background: Exercise could contribute to weight loss by altering the sensitivity of the appetite regulatory system.