Leptin In the mid 1980's Amgen bought the rights to study the leptin molecule, the key regulator of fat stores. It was thought to have great potential for treating obesity. The excitement surrounding leptin was based on several studies that showed that when leptin was injected into mice and rats with genetically based obesity, it caused them to decrease food intake and drop to a normal weight with no side effects. The higher the leptin levels in the blood serum, the more pronounced the effect was. There seemed to be great potential for therapeutic uses of leptin. A setback occurred with the finding that most people with non-genetically based obesity had higher than normal levels of leptin in their blood, which would seem to be in conflict with the weight-reducing effect of high leptin in the rodent studies. It was theorized that obese people might become resistant to their own leptin in a way analogous to obese people who develop diabetes because they become resistant to their own insulin.
Subsequent clinical trials where leptin was administered to obese people showed no significant weight loss. It was thought that leptin was not crossing the blood-brain barrier in order to affect its target organ, the brain.
Leptin Regulation: Leptin is a 16 kDa protein expressed exclusively in adipose tissue. It is a hormone that communicates the status of energy stores to the hypothalamus. Higher leptin levels correlate with energy expenditure and low leptin levels correlate with energy saving (2-4; 12-15). Low leptin levels are found in rodents with the leptin gene (ob gene) knocked out and in people with mutations in the ob gene (14).
Several factors contribute to leptin levels. The most important contribution is the amount of body fat, but age, gender, hormones and cytokine levels also have an effect...