Abstract
Hypothalamic Leptin Resistance: From BBB to BBSome.
Highlights
The role of leptin in human obesity remains poorly understood
Central leptin resistance may develop via different mechanisms (Fig 1), such as (1) impairment in the function of the saturable leptin transporters in the blood– brain barrier (BBB) [7]; (2) deficient leptin signaling [4,5,7,8]; (3) lipotoxicity and endoplasmic reticulum (ER) stress, as well as (4) inflammatory signals that have been shown to modulate leptin responsiveness [9]
BBS mouse models recapitulate many of the characteristics found in patients, including obesity, which is associated with hyperphagia and leptin resistance
Summary
The role of leptin in human obesity remains poorly understood. Leptin deficiency and mutations in leptin receptor cause morbid obesity; these defects are extremely rare [6]. BBS mouse models recapitulate many of the characteristics found in patients, including obesity, which is associated with hyperphagia and leptin resistance. Some mice showed altered hypothalamic expression of POMC [14], indicating that the primary effect leading to positive energy balance might imply altered central leptin action.
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