Introduction: Fat free mass, of which skeletal muscle is a major component, correlates positively with energy intake at energy balance. This is due to the effects of metabolically active tissue on energy expenditure which in itself appears to signal to the brain a drive to eat to ensure cellular energy homeostasis. The mechanisms responsible for this drive to eat are unknown but are likely to be related to energy utilisation. In this context muscle imparts an indirect influence on hunger. The drive to eat is also enhanced after muscle loss secondary to intentional weight loss. The evidence is from starvation studies where loss of both fat mass and skeletal muscle mass directly influences the trajectory and magnitude of weight regain highlighting their potential role in long term appetite control. The mechanisms responsible for the potential direct drive to eat stemming from muscle loss is unknown. Areas covered: Here we review the literature pertaining to muscle and appetite at both energy balance and after weight loss. A literature search was conducted to identify studies related to appetite, muscle, exercise and weight loss. Expert opinion: Understanding the mechanisms which link energy expenditure and muscle loss to hunger has the potential to positively impact both the prevention and the treatment of obesity. This is an understudied area and as such potential mechanisms which increase hunger remain speculative.

Efficacy of obesity treatments varies between individuals, highlighting the presence of responders and non-responders. Whilst exercise alone or exercise combined with diet leads to underwhelming weight loss for most, there exist super responders losing significant weight. Furthermore, in response to weight loss, the majority but not all patients tend to regain weight. Within the biopsychosocial model, biology as a determinant of response has been underappreciated. The understanding of the role that organs beyond adipose tissue and the gastrointestinal tract play in appetite control and body weight regulation has developed in recent years. The aim of this review is to highlight potential myokines that may be important in appetite physiology and overall energy balance. A number of attractive targets are described that warrant further investigation. A deeper understanding of how these myokines may drive feeding behaviours has the potential to improve measures to prevent and treat obesity through a precision medicine approach.