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While putative feedback signals arising from adipose tissue are commonly assumed to provide the molecular links between the body's long-term energy requirements and energy intake, the available evidence suggests that the lean body or fat-free mass (FFM) also plays a role in the drive to eat. A distinction must, however, be made between a 'passive' role of FFM in driving energy intake, which is likely to be mediated by 'energy-sensing' mechanisms that translate FFM-induced energy requirements to energy intake, and a more 'active' role of FFM in the drive to eat through feedback signaling between FFM deficit and energy intake. Consequently, a loss of FFM that results from dieting or sedentarity should be viewed as a risk factor for weight regain and increased fatness not only because of the impact of the FFM deficit in lowering the maintenance energy requirement but also because of the body's attempt to restore FFM by overeating-a phenomenon referred to as 'collateral fattening'. A better understanding of these passive and active roles of FFM in the control of energy intake will necessitate the elucidation of peripheral signals and energy-sensing mechanisms that drive hunger and appetite, with implications for both obesity prevention and its management.

Passive and active roles of fat-free mass in the control of energy intake and body composition regulation