@article{oai:nagasaki-u.repo.nii.ac.jp:00000380,
 author = {Kinoshita, Ayaka and Hayashi, Hiroko and Kusano, Natsuko and Inoue, Shun and Komatsu, Toshimitsu and Mori, Ryoichi and Park, Seongjoon},
 issue = {1},
 journal = {Acta medica Nagasakiensia},
 month = {Nov},
 note = {Background: The incidence of hepatocellular carcinoma (HCC) with fatty liver disease has been increasing, and the sympathetic nervous system may be involved in hepatocarcinogenesis in such cases. Here we analyzed the impact of 
neuropeptide Y (Npy), which is released from sympathetic nerve endings, on hepatocarcinogenesis in different nutritional settings. 
Methods: Hepatocellular carcinoma was induced by an intraperitoneal injection of diethylnitrosamine (DEN) in male C57BL6/J 
mice null for Npy gene (Npy?/?) and their haplotype (Npy+/?) as a control (Ctrl). The mice were subjected to one of three dietary 
regimens: ad libitum feeding with a standard diet (AL) or a high-fat diet (HFD), or 30% dietary-restricted feeding (DR). 
Results: The occurrence and growth of HCC were accelerated in the Npy?/? mice, particularly in the AL and HFD conditions. 
Steatosis was promoted at 28 wks in the Npy?/? mice; steatohepatitis was not exacerbated in the Npy?/? mice at 28 or 48 wks. 
The alterations in the TNFα- and IL-6-mRNA expression levels and phosphorylated NF-κB and ERK1/2 levels in the liver at 28 
wks did not support the current paradigm of a steatohepatitis-HCC sequence. By contrast, the DR inhibited steatohepatitis and 
then hepatocarcinogenesis even in the Npy?/? mice, although the Npy?/?-DR mice displayed peculiar findings, i.e., the activation 
of TNFα-NF-κB signaling, a possible protective mechanism against the elevated cell proliferation and genotoxic stresses. 
Conclusions: Npy exerts an inhibitory effect on the occurrence and growth of HCC, particularly in overnutrition. Npy is also 
dispensable for the tumor-inhibiting effect of DR. The activation of Npy could be a promising target for the prevention of HCC., Acta medica Nagasakiensia, 63(1), pp.11-25; 2019},
 pages = {11--25},
 title = {Neuropeptide Y inhibits hepatocarcinogenesis in overnutrition in mice},
 volume = {63},
 year = {2019}
}