initial fat mass, and later allowed to eat freely, they reattained and even surpassed their original fat levels, reaching 145% of the pre-starvation fat levels. Evidence for an organism-level set point has been found experimentally in "normal" rats and in rats with dorsomedial hypothalamic lesions. In addition, in a study with obese and non-obese subjects who lost 10%–20% of their body mass from underfeeding, the energy expenditure of the subjects was found to decrease, while after gaining 10% of their body mass from overfeeding their energy expenditure was found to increase. Mechanism As there has not been one unique mechanism identified to be behind weight regulation, it is likely that there are multiple factors reaching a shared equilibrium that result in a stable bodyweight. Leptin is known to play a key role in appetite and thus weight regulation, and may be important in regulating the set point and regulating body weight towards the set point. Changing leptin levels – either associated with weight gain or loss, or induced via central or peripheral administration in animal models – directly alter feeding behaviour and energy expenditure. Individuals who, due to genetic mutation, are unable to produce functional leptin or who produce leptin but are insensitive to it are prone to develop obesity. This has been confirmed by experimental "knockdown" of leptin receptors in the lateral hypothalamus in rats, which caused the rats to consume more calories and increase in body weight compared to control rats. However, most human obesity is not linked to failure to normally process leptin. Criticism and alternatives While set point theory has been supported in animals and humans, it may not apply to humans eating a western diet, which may be obesogenic to an extent that it overcomes the homeostatic process set forth in set point theory. Set point theory does not on its own explain why body mass index for humans, measured as a proxy for fat, tends to change with increasing age or why obesity levels in a population vary depending on socioeconomic or environmental factors (or why weight tends to change for an individual when socioeconomic status and environment change). One alternative to set point theory is settling points. With settling points, an increase (or decrease) in calories consumed leads to an increase (or decrease) or energy expended until an equilibrium is reached; this differs from the set point theory in that the increase (or