Health: mechanism underlying the relationship between sleep deprivation and obesity discovered
A recent study conducted by Italian researchers sheds new light on the already known correlation between prolonged sleep deprivation and obesity. The study suggests a defective functioning of an ancestral mechanism involved in the production of a hormone called orexin-A which promotes wakefulness and alertness during food seeking.
The association between sleep and obesity, already known to researchers, may be explained by a recent Italian study. The study, led by Luigia Cristino, a researcher from the CNR Institute of Biomolecular Chemistry in Pozzuoli (ICB-CNR), in collaboration with CEINGE – Advanced Biotechnology, the CNR Institute of Protein Biochemistry (IBP-CNR), the Federico II University of Naples and the Carlo Bo University of Urbino, was published in PNAS.
The results achieved suggest that obese people show a defective functioning of an ancestral mechanism that in animals is activated to ensure survival, which is based on the production of orexin-A: a 33-amino-acid peptide that, from the evolutionary point of view, promotes wakefulness and alertness during food seeking. In particular, researchers discovered the role of orexin-A in inducing the synthesis of endocannabinoid 2-AG, which is involved in hunger activation.
“Endocannabinoids are small signalling molecules that use the same membrane receptors to which also the main psychotropic constituent of cannabis binds, i.e. THC (Δ9-tetrahydrocannabinol). It was already known that endocannabinoids stimulate appetite, and this was largely shown by our studies”, explained Luigia Cristino. “However, the novelty of this study is that we discovered that orexin-A is a strong inducer of the synthesis of 2-AG which, in turn, activates the CB1 receptor of the endocannabinoid system in the POMC hypothalamus neurons, thus inhibiting the production of a-MSH, another hormone which blocks hunger”. This mechanism, which in individuals with normal weight ensures a correct energy intake during wakefulness, is defective in obese people due to the malfunctioning of the leptin hormone: the main hunger suppressor. “This malfunctioning triggers a vicious circle involving the increase of appetite and body weight which leads to the point of no return where the brain can no longer switch off the feeling of hunger”, continued the researcher.
The researchers’ conclusions, supported by the inverse correlation between circulation levels of orexin-A and a-MSH found in the blood of obese adult males, pave the way to possible therapeutic solutions. “In this scenario, the study shows that orexin-A receptors are very good pharmacological targets that can be blocked in order to fight obesity and its comorbidities in an era in which the evolutionary history of man has, paradoxically, led us to switch from the need for eating to survive to the need for fasting to live fit”, concluded Vincenzo Di Marzo, ICB-CNR researcher.