The discovery of adipocyte-derived leptin in 1994 quickly led to the recognition of this hormone as a key to understanding the homeostatic regulation of body weight (Zhang et al., 1994). Leptin is expressed in proportion to body fat, suppresses food intake, and prevents low metabolism, thereby promoting weight loss overall. In turn, negative energy balance suppresses leptin levels enabling weight gain (Schwartz et al., 2000). Yet, the initial high hopes that leptin treatment could cure obesity were not fulfilled due to the paradoxical observation that obesity is already associated with high leptin levels (Considine et al., 1996), which can cause leptin resistance (El-Haschimi et al., 2000), while lack of leptin also results in severe obesity (Pelleymounter et al., 1995).
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