Leptin responses to overfeeding: Relationship with body fat and nonexercise activity thermogenesis

Administration of leptin to rodents results in weight loss through decrease d food intake and increased energy expenditure that occurs in part through increased spontaneous activity. In humans, low levels of spontaneous physic al activity and below normal plasma leptin concentrations predict subsequen t excess weight gain. We recently found that failure to increase nonexercis e activity thermogenesis (NEAT) with overfeeding results in greater fat gai n in humans, and subsequently evaluated whether changes in leptin are relat ed to NEAT activation. We measured plasma leptin concentrations and adipose tissue leptin messenger ribonucleic acid together with the components of e nergy expenditure in 16 nonobese humans before and after overfeeding to ass ess the relationship between leptin responses to overfeeding and the change s in NEAT. Adipocyte leptin expression was up-regulated with overfeeding, a nd leptin concentrations increased. Leptin concentrations correlated with b ody fat before and after overfeeding. Changes in leptin with overfeeding we re strongly related to changes in body fat, but not to changes in NEAT. Cha nges in NEAT correlated inversely with fat gain. It is, therefore, unlikely that leptin mediates activation of NEAT with overfeeding in nonobese human s; rather, leptin directly reflects body fat mass and fat mass gain.