Leptin: Function


Contents


Function



Leptin is produced by adipose tissue. The more adipose tissue and animal has the more leptin is cirulated in the blood stream. It is thought that obesity is a direct result from the disfunction or mutation of leptin receptors.

The circulating leptin informs the brain of body fat. Leptin promotes weight loss by suppressing appetite and stimulating metabolism. Neuropeptide Y (NPY), abundant in the hypothalamus, is responsible for the feeling of hunger. The expression and release of NPY is inhibited by leptin. As weight is gained the leptin levels are increased. This inhibits the function of NPY creating a response to obesity. Food intake is decreased, energy expeniture is increased, the sympathetic activity is increased. On the other hand as weight is lossed, there is a decrease in leptin circulation, which increases the effect of NPY causing a response to starvation. The animals appetite is increased. The animal will reduce unecessary energy expenditure, including reproductive function. The overall temperature of the animal is decreased, and there is an increase in parasympathetic activity.

Leptin serves as an intracellular messanger as well. The amount of leptin in the body will directly influence the amount of leptin that is produced by adipose tissue. Diabetic and obeses mice usually have disfunctional leptin or no leptin at all in the blood stream. This is done by the leptin binding to a leptin receptor. The receptor is a class 1 cytokine. The leptin receptor is a cellular surface protein. This complex of leptin and the receptor servers as an intracellular signaling device. This complex is responsible for communication with the adipose cell, which signals the production or the stop the production of leptin, depending on the concentration of leptin. If the receptor is mutant, then it is impossible to signal for the cell to stop growing and producing leptin. If leptin is not produced the animal can then become obese.

Leptin functions along with NPY to regulate apetite. NPY functions in the hypothalamus. As NPY levels are increased the apetite is reduced. Leptin also binds to the same site as NPY. If an animal is over-producing leptin then the binding sites in the hypothalamus is covered with leptin instead of NPY. This leads to an apetite that is never reduced, which in turn causes obesity.

Leptin has been linked to other hormonal functions as well. Evidence has shown that leptin appears to signal the onset of puberty. Female mice that are treated with leptin speed up the process of sexual maturity. This again is closely realted to starvation as well. As leptin levels decrease, the starvation response decreases the activity of unnecessary bodily functions such as reproduction. Reasearchers have not yet worked out how leptin levels bring about starvation-induced hormonal changes. Some work suggest that they may lead to increased activity of an important regulator of stress hormone production. They have found that normal leptin levels damp down production of a brain peptide called corticotropin-releasing hormone that works throgh the pituitary gland to boost production of adrenal steroids.

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References



1. Gura, T. Science vol. 275, 7 Feb. 1997. 751-753. 2. Friedman, J. Nature. vol. 385, 9 Jan. 1997, 119-121. 3. Erickson, J., Hollopeter, G., Palmiter, R. Science. vol. 274. 6Dec. 1996, 1704-1706. 4. Howlett, R. Nature. vol 382, 11 July 1996, 113. STRUCTURE | FUNCTION | REGULATION/CONTROL