What is leptin?
Leptin (from the Greek root leptos meaning lean) is a small protein-like hormone, discovered in 1994 by Friedman. It is encoded by the obesity gene (OB), has a molecular weight of 16 KDa and is strongly involved in the regulation of lipid metabolism and energy consumption.
Functions and properties
The discovery of leptin confirmed the existence of a communication channel between adipose tissue and brain, which aims to regulate the accumulation of fat in adipocytes. When lipid reserves increase, white fat cells accelerate leptin synthesis to signal the hypothalamus that food intake must be reduced.
Leptin decreases the sense of hunger (anorectic effects) and increases energy expenditure, favoring the reduction of body weight and fat mass.
Conversely, when adipose reserves decrease, white adipocytes reduce leptin synthesis to signal the hypothalamus that food intake must be increased and energy expenditure reduced.
Under normal conditions, leptin levels:
- they increase after a meal and are reduced in prolonged fasting;
- they are proportional to the fat mass present in the body (higher in the obese, less in thin people). However, the latter are more sensitive to the action of the hormone.
Other functions
In addition to regulating the sense of satiety, leptin also intervenes in the regulation of numerous biological functions:
- regulates thyroid activity;
- facilitates hematopoiesis;
- it regulates the immunological system (leptin enhances the immune system to trigger real autoimmune diseases);
- regulates the reproductive system (promotes the secretion of gonadotropins; it is also produced by the placenta);
- regulates bone formation.
Therapeutic Potentials
Experiments on laboratory mice gave the following results:
- the administration of leptin reduces food intake and increases energy expenditure;
- mice lacking the obesity gene, therefore unable to produce leptin, become obese, as well as those with defective hormone receptors.
Despite the positive results obtained in laboratory mice, the total efficacy of leptin in the treatment of human obesity has never been proven. Indeed, there are rare cases of absence of the OB gene, while more often obese people have high plasma concentrations of leptin. Hence the hypothesis that obesity is associated with a resistance to the action of this appetite modulator. In other words, the hypothalamic receptors of most obese people are not very sensitive to the action of the hormone. And the bad news does not end there. Scholars have in fact noticed that in obese people hypothalamic receptors, although they are not able to understand the message of abstinence of food due to the high levels of leptin, are nevertheless sensitive to the decrease in the concentration of the hormone. For this reason:
- when an obese fat the leptin stimulus is "ignored" and with it also its anorexigenic action;
- on the contrary, when an obese tries to lose weight the hypothalamus receives the decrease in leptin and pushes the individual in search of food.
The problem, therefore, is not given by a leptin defect but by a reduced receptor sensitivity towards it. All this has considerably reduced the therapeutic potential of leptin in the treatment of obesity. Currently the research is focusing on the synthesis of hormone analogues and on alternative methods of administration able to overcome the increased resistance to leptin.
Finally, it is worth remembering that in humans food intake is a very complex phenomenon, because it is mediated by numerous biological signals that are integrated hypothalamically but also by non-energetic factors (cultural, social, emotional, etc.).
