A new mechanism of appetite regulation

Korean scientists have discovered a previously unknown mechanism of regulation of eating behavior associated with the coenzyme tetrahydrobiopterin (BH4).

Denis Strigun, Naked Science

The hypothalamus is responsible for the regulation of eating behavior in mammals. The saturation center and the hunger center located in it are innervated by neurons of a higher structure – the arcuate nucleus – through the cleavage product of proopiomelanocortin and neuropeptide Y, respectively. At the same time, signals about a sufficient level of energy enter the hypothalamus from adipose tissue and the digestive system, including through the hormone leptin.

The synthesis of leptin by adipose tissue cells determines the overall control of appetite. In turn, the depletion of fat reserves leads to the cessation of hormone synthesis and the initiation of eating behavior. By binding to the neurons of the arcuate nucleus, leptin inhibits the production of neuropeptide Y and stimulates the synthesis of proopiomelanocortin, suppressing appetite. However, some overweight people do not have leptin deficiency. Therefore, scientists suggest that adipose tissue can regulate its replenishment in other ways.

In a new paper, researchers from the Korean Institute of Science and Technology studied the mechanism of regulation of eating behavior in Drosophila (Drosophila melanogaster). This model organism was chosen due to its accessibility and simplicity of genetic manipulation. In order to trace the feedback between the brain and adipose tissue, the authors searched for molecular targets, the "shutdown" of which would cause changes in the mechanism. According to the analysis, the suppression of genes encoding enzymes for the synthesis of tetrahydrobiopterin (BH4) in adipose tissue led to the fact that animals began to consume more sweetened water and actively store fat. Suppression of BH4 synthesis in the brain led to similar results, while the "shutdown" of peptide F receptors (orthologue of neuropeptide Y) normalized the appetite of flies.

Scheme of appetite regulation through inhibition of neuropeptide F by tetrahydrobiopterin

Further experiments have shown that BH4 regulates appetite by inhibiting the release of neuropeptide F, whereas its synthesis is carried out at the expense of adipose tissue. The mechanism of the latter remains unclear, but scientists have found that reducing the caloric content of food increases the volume of its consumption and suppresses the expression of BH4 synthesis enzymes. In other words, in this case, the system is in equilibrium and responds better to incoming energy.

Meanwhile, in humans, violations of BH4 synthesis can cause severe diseases, in particular mental retardation and phenylketonuria. Tetrahydrobiopterin-based drugs can alleviate the corresponding symptoms. So far, none of the researchers have evaluated the association of BH4 with obesity in humans.

Article by Kim et al. A fat-derived metabolite regulates a peptidergic feeding circuit in Drosophila published in the journal PLoS Biology.

Portal "Eternal youth" http://vechnayamolodost.ru  04.04.2017