Examining the biological mechanisms that underlie the drive to eat in humans

Aim: Integrate whole-body and tissue-organ composition with physiological and psychological measures of appetite during prolonged energy deficit to explain the mechanisms underpinning the drive to eat and provide new insight into the appetitive mechanisms that oppose weight loss.

Rational: A current weakness in our understanding of human appetite is the inability to adequately explain the biological mechanisms underpinning the drive to eat (e.g., hunger), which undermines our attempts to manage appetite during periods of under-and-over-nutrition. Current scientific approaches focus on appetitive signals from adipose tissue and the GI tract, but these signals primarily account for feelings of satiety rather than the mechanisms that drive hunger. We have recently provided novel evidence that the metabolic activity of fat-free mass creates a drive to eat that ensures the energy needs of key tissues and organs are met. This provides a theoretical framework to examine the relationships between body structure, composition, and physiological function, and the way these interactions influence key psychological and behavioural determinants of appetite. Positioning fat-free mass as key feature of appetite also provides new opportunities to understand how changes in appetite oppose that weight loss, and develop novel strategies that limit the drive to eat rather than enhance satiety to prevent overeating. Increases in hunger is also one of the key reasons why individuals fail to maintain weight loss over time, but such changes in hunger are inconsistent and current biological explanations fail to fully explain why. We have recently shown that the amount of fat-free mass lost during weight loss promotes increased hunger and weight regain, but the consequences of fat-free mass loss on the psychological and behavioural determinants of appetite have largely ignored.

Design: A dietary weight loss trial in individuals with overweight or obesity will be used to induce 10% weight loss. Tissue-organ (MRI) and whole-body composition (DEXA & 4-compartmental model), resting and total daily energy expenditure (indirect calorimetry & doubly labelled water), and physiological (appetite-related hormones) and psychological appetitive processes (subjective appetite, eating behaviour traits, food reward) will be measured at baseline, post-weight loss and following weight stabilisation to allow links to be made between physiological, psychological and behavioural determinants of appetite. To bridge the gap between laboratory and free-living environments, energy balance tracking technology will be used to quantify weekly changes in energy intake and energy expenditure during weight loss, based on free-living energy expenditure (accelerometery), body weight (Bluetooth scales) and validated intake-balance models of energy intake. Subjective appetite, food reward and state/trait measures of eating behaviour will be remotely measured each week to capture changes in the motivation to eat in the free-living environment.