Nesfatin-1: a new hormone in the control of food intake and the mechanism of damage and protection of gastric mucosa

Nesfatin-1 is an 82-amino-acid peptide derived from posttranslational processing of the N-terminal fragment of nucleobindin 2 (NUCB2), a protein precursor for nesfatin-1, which is highly conserved across mammalian species. The expression of NUCB2/nesfatin-1 has been detected in the stomach, most prominently within ghrelin cells of the rat gastric oxyntic mucosa. The first biological action ascribed to NUCB2 and nesfatin-1 was the reduction of dark-phase food intake with a concomitant reduction in body weight gain when these peptides were injected intracerebroventricularly, suggesting their anorexigenic action in rodents. Studies on the potential physiological importance of nesfatin-1 have shown that nesfatin-1, similarly as for other appetite peptides such as ghrelin and leptin studied before, exerts protective activity against gastric mucosal lesions induced by topical damaging agents and seems to be also effective against those caused by stress. This gastroprotective action of exogenous nesfatin-1 may involve the activation of PG/COX and NO/NOS systems, resulting in an increase in gastric blood flow accompanied by a rise in plasma nesfatin-1 levels. Thus, it is concluded that 1) endogenous PG and NO may mediate the nesfatin-1-induced gastroprotection in the rat stomach, and 2) clinical studies regarding the potential benefit of nesfatin-1 observed in animals should shed more light on the efficacy of this peptide to prevent gastric disorders including the formation of gastric microbleeding in humans.