Role of neuromedin U in accelerating of non-alcoholic steatohepatitis in mice

•Neuromedin U (NMU) and NMU receptor 1 (NMUR1) are undetectable in normal liver.•In NASH, NMU and NMUR1 production is increased with inflammation.•Hepatic NMU overexpression exacerbates NASH pathogenesis. Neuromedin U (NMU), a neuropeptide originally isolated from porcine spinal cord, has multiple p...

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Bibliographic Details
Published in:Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2018-01, Vol.99, p.134-141
Main Authors: Teranishi, Hitoshi, Hayashi, Masafumi, Higa, Ryoko, Mori, Kenji, Miyazawa, Takashi, Hino, Jun, Amano, Yuichiro, Tozawa, Ryuichi, Ida, Takanori, Hanada, Toshikatsu, Miyazato, Mikiya, Hanada, Reiko, Kangawa, Kenji, Nakao, Kazuwa
Format: Article
Language:English
Subjects:
Animals
Gene Expression Regulation
Inflammation
Liver - metabolism
Liver - pathology
Male
Mice
Mice, Inbred ICR
NAFLD/NASH
Neuromedin U
Neuropeptides - biosynthesis
Neuropeptides - chemistry
Neuropeptides - pharmacology
Non-alcoholic Fatty Liver Disease - metabolism
Non-alcoholic Fatty Liver Disease - pathology
Obesity - metabolism
Obesity - pathology
Obesity-related disease
Receptors, Neurotransmitter - metabolism
Swine
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Summary:•Neuromedin U (NMU) and NMU receptor 1 (NMUR1) are undetectable in normal liver.•In NASH, NMU and NMUR1 production is increased with inflammation.•Hepatic NMU overexpression exacerbates NASH pathogenesis. Neuromedin U (NMU), a neuropeptide originally isolated from porcine spinal cord, has multiple physiological functions and is involved in obesity and inflammation. Excessive fat accumulation in the liver leads to non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), which is closely associated with obesity. NAFLD and NASH develop and progress via complex pathophysiological processes, and it remains unclear to what extend the NMU system contributes to the risk of obesity-related disorders such as NAFLD and NASH. Here, we demonstrate that the NMU system plays a role in NAFLD/NASH pathogenesis. In the normal mouse liver, NMU mRNA was not detectable, and expression of the mRNA encoding neuromedin U receptor 1 (NMUR1), the peripheral receptor of NMU, was low. However, the expression of both was significantly increased in the livers of NASH mice. Furthermore, overproduction of NMU induced the mouse liver by hydrodynamic injection, exacerbated NASH pathogenesis. These data indicate a novel role for the peripheral NMU system, providing new insights into the pathogenesis of NAFLD/NASH.
ISSN:0196-9781
1873-5169
DOI:10.1016/j.peptides.2017.09.011