Hormones secreted by adipocytes
Leptin, adipocyte origin
Leptin, anorectic protein of adipocyte origin was discovered in 1994. It acts primarily in the central nervous system in, in particular the hypothalamus.
Leptin ( from the Greek leptos which means thin) or protein OB, thus called because it initially was isolated in obese mice, is a polypeptide of 167 amino acids (1600 daltons) secreted by the adipocytes, released in blood, crossing the blood-brain barrier and activating receptors which are principally located at the level of the hypothalamus.
Leptin secretion increases statistically with the adipose tissue mass (i.e. it is higher in obese patients).
The activation of leptin receptors brings into play the signaling pathway JAK/STAT, Janus kinase/signal transducer and activator of transcription, leading to modifications of transcription. The principal effect of leptine is to reduce appetite and to increase thermogenesis, by modifications of the expression of alpha-MSH, CART, AgRP and NPY leading in particular to stimulation of the sympathetic system. Leptin has other effects less well known, it could reinforce the action of insulin, could be involved in triggering puberty.
Incertain obese patients, a deficiency in leptin can exist but this is exceptional. Generally, there is a disorder of its penetration into the brain or an anomaly of its receptors and an excess of secretion of neuropeptide Y (NPY) which induces food intake.
Congenital leptin deficiency in human beings is exceptional but, when it exists, the administration of leptin has remarkable effects, it reduces obesity, hyperphagia and induces the onset of puberty if it is delayed.
Adiponectin
Adiponectin, protein of 247 amino acids, secreted exclusively by the adipocyte and present in the plasma, potentiates the effects of insulin.
The plasma concentration of adiponectin, compared to controls, is lowered in diabetics, obese patients and patients with coronary diseases.
Adiponectin activates 2 types of receptors called AdipoR1 present in the majority of the cells but particularly in the skeletal muscle and AdipoR2 present in the liver. The stimulation of these receptors activates, inter alia, the signaling pathway AMPK,adenosine monophosphate kinase. Adiponectin increases the translocation of carriers GLUT4 of the cytoplasm towards plasma membrane and thus facilitates glucose uptake by tissues. It decreases the production of glucose by the liver and increases the oxidation of fatty acids. It decreases insulin resistance. It decreases the release of pro-inflammatory cytokines such as TNF alpha.
Glitazones and sibutramine (see http://www.pharmacorama.com/ezine/sibutral.php) increase the plasma concentration of adiponectin.
Resistin, adipocyte origin
Resistin is a protein of 114 amino acids, rich in proline and cystein, secreted by adipocytes and macrophages in human beings. It was called thus because it was supposed to be, at least partially, responsible of insulin resistance. The data about resistin are too limited and sometimes too conflicting to make it possible to draw practical conclusions.
Adiponectin and resistin do not seem implicated in the regulation of dietary intake.
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