Body weight is related to fat mass, which is associated with obesity. Our study explored the effect of fat-1 gene on body weight in fat-1 transgenic mice. In present study, we observed that the weight/length ratio of fat-1 transgenic mice was lower than that of wild-type mice. The serum levels of triglycerides (TG), cholesterol (CT), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and blood glucose (BG) in fat-1 transgenic mice were all decreased. The weights of peri-bowels fat, perirenal fat and peri-testicular fat in fat-1 transgenic mice were reduced. We hypothesized that increase of n-3 PUFAs might alter the expression of hypothalamic neuropeptide genes and lead to loss of body weight in fat-1 transgenic mice. Therefore, we measured mRNA levels of appetite neuropeptides, Neuropeptide Y (NPY), Agouti-related peptides (AgRP), Proopiomelanocortin (POMC), Cocaine and amphetamine regulated transcript (CART), ghrelin and nesfatin-1 in hypothalamus by real-time PCR. Compared with wild-type mice, the mRNA levels of CART, POMC and ghrelin were higher, while the mRNA levels of NPY, AgRP and nesfatin-1 were lower in fat-1 transgenic mice. The results indicate that fat-1 gene or n-3 PUFAs participates in regulation of body weight, and the mechanism of this phenomenon involves the expression of appetite neuropeptides and lipoproteins in fat-1 transgenic mice.