Discovery of nesfatin-1 and overview of biological actions and new developments

Obesity arises from an impairment of energy homeostasis, which essentially involves the balance of food intake and energy dissipation. Some secreted molecules in the hypothalamus have become the focus of recent attention for their important roles in the regulation of food intake. One such molecule, nesfatin-1, is a novel molecule originally expressed in the hypothalamic nuclei of the brain, which exerts its satiety function in conjunction with other molecules, including oxytocin and pro-opiomelanocortin (POMC). Nesfatin-1 is processed from its precursor, DNA binding/EF-hand/acidic protein (NEFA)/nucleobindin 2 (NUCB2), and its mRNA is unexpectedly stabilized by troglitazone, a ligand for peroxisome proliferator-activated receptor γ (PPARγ). Subsequent analyses and observations have demonstrated that nesfatin-1 is also located in brain nuclei outside the hypothalamus and in peripheral tissues, and that nesfatin-1 neurons in the brain receive several signals. These findings imply that nesfatin-1 is an endogenous molecule important for the regulation of not only food intake but also other physiological functions. We discuss what is currently known about nesfatin-1, including new developments in our understanding of its distribution, regulation, and biological function.