Since NUCB2 was discovered, the information about NUCB2/nesfatin-1 in appetite regulation in both mammals and teleost has been still limited. The present study aims to determine the effects of nesfatin-1 on food intake and to explore the appetite mechanism in Siberian sturgeon. In this study, nucb2 cDNA sequence of 1571bp was obtained, and the mRNA expression of nucb2 was abundant in brain and liver. Levels of nucb2 were appreciably increased in brain after feeding 1 and 3h, while significantly decreased within fasting 15days. Except for fasting 1day, the expression pattern of nucb2 in the liver was similar to the brain. Acute intraperitoneal (i.p.) injection of nesfatin-1 inhibited the food intake during 0–1h in a dose-dependent manner and 50 or 100ng/g BW nesfatin-1 significantly decreased the cumulative food intake during 3h. The daily food intake and cumulative food intake were remarkably reduced post chronic (7days) i.p. injection. Moreover, chronic i.p. injection of nesfatin-1 affected the expression of appetite factors including cart, apelin and pyy in the brain, stomach and liver with the consistent pattern of change, while the levels of cck, ucn3 and nucb2 in these have different patterns. This study demonstrates that nesfatin-1 acts as a satiety factor in reducing the short-term and long-term food intake of Siberian sturgeon. Therefore, the data suggesting nesfatin-1 inhibits the appetite through different signal pathways in the central and peripheral endocrine systems of Siberian sturgeon.