It is estimated that somewhere between 34 and 61 million people in the US are obese and in much of the developing world incidence is increasing by about 1% per year. Obesity increases the likelihood of death from all causes by 20%, and more specifically death from coronary artery disease and stroke are increased by 25% and 10% respectively. Key priorities of anti-obesity treatments are to reduce food intake and/or hyperlipedia however molecules that have the additional effect of reducing insulin resistance, a primary factor contributing to the development of diabetes, would have added benefit. In a recent dossier overviewing therapeutic targets developed to break the link between obesity and diabetes (click here for access) we describe the potential of leptin agonists. Leptin agonists have recently been shown to not only reduce body weight and glucose levels in obese animals but also to increase insulin sensitivity. Given the anorectic properties of leptin it is therefore perhaps paradoxical that obese humans have significantly elevated plasma leptin concentrations compared with lean individuals. However the ratio of CSF leptin levels to serum leptin levels has recently been shown to be 4 times greater in lean individuals than in obese individuals. One interpretation of this finding is that human obesity could be secondary to a central resistance to leptin action, causing a relative leptin deficiency in the CNS. In order that the potential of leptin as a therapeutic target may be exploited it is crucial that leptin entry into the CNS is better understood. Further, targeting the mechanisms that control leptin uptake may offer alternative approaches to the direct strategy of administering leptin mimics. A recent review by field-leading leptin researchers describing leptin access to the CNS is thus considered important reading for researchers involved in metabolic disease or CNS research.

Limited brain access for leptin in obesity. Couse et al, Pituitary 2001 Jan-Apr;4(1-2):101-10

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