Fat-free mass and resting metabolic rate drive daily energy intake through an excitatory tonic signal, whereas fat mass provides an inhibitory signal that weakens in obesity due to leptin resistance, creating a mismatch that promotes overconsumption.

Blundell et al. (68) has recently proposed that the energy expenditure arising from fat-free mass, as the main determinant of resting metabolic rate (74), represents a physiological source of hunger that drives food intake at a level proportional to basal energy requirements... the progressive accumulation of adipose tissue with obesity development would lead to leptin (and insulin) resistance, attenuating the strength of this tonic inhibition. In contrast however, the tonic drive to eat stemming from fat-free mass and resting metabolic rate, which are elevated in the obese state, would remain unabated.