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Damage to enteric neurons occurs in mice that develop fatty liver disease but not diabetes in response to a high-fat diet

journal contribution
posted on 2014-08-01, 00:00 authored by Leni RiveraLeni Rivera, C Leung, R V Pustovit, B L Hunne, S Andrikopoulos, C Herath, A Testro, P W Angus, J B Furness
Background Disorders of gastrointestinal functions
that are controlled by enteric neurons commonly
accompany fatty liver disease. Established fatty liver
disease is associated with diabetes, which itself
induces enteric neuron damage. Here, we investigate
the relationship between fatty liver disease and
enteric neuropathy, in animals fed a high-fat, highcholesterol
diet in the absence of diabetes. Methods
Mice were fed a high-fat, high-cholesterol diet (21%
fat, 2% cholesterol) or normal chow for 33 weeks.
Liver injury was assessed by hematoxylin and eosin,
picrosirius red staining, and measurement of
plasma alanine aminotransaminase (ALT). Quantitative immunohistochemistry was performed for different
types of enteric neurons. Key Results The mice
developed steatosis, steatohepatitis, fibrosis, and a 10-
fold increase in plasma ALT, indicative of liver
disease. Oral glucose tolerance was unchanged. Loss
and damage to enteric neurons occurred in the myenteric
plexus of ileum, cecum, and colon. Total numbers
of neurons were reduced by 15–30% and neurons
expressing nitric oxide synthase were reduced by
20–40%. The RNA regulating protein, Hu, became
more concentrated in the nuclei of enteric neurons
after high-fat feeding, which is an indication of stress
on the enteric nervous system. There was also disruption
of the neuronal cytoskeletal protein, neurofilament
medium. Conclusions & Inferences Enteric
neuron loss and damage occurs in animals with fatty
liver disease in the absence of glucose intolerance. The
enteric neuron damage may contribute to the gastrointestinal
complications of fatty liver disease.

History

Journal

Neurogastroenterology & motility

Volume

26

Issue

8

Pagination

1188 - 1199

Publisher

Wiley-Blackwell

Location

Chichester, Eng.

ISSN

1350-1925

Language

eng

Publication classification

C Journal article; C1.1 Refereed article in a scholarly journal

Copyright notice

2014, John Wiley & Sons