High fat diet induced hepatic steatosis establishes a permissive microenvironment for colorectal metastases and promotes primary dysplasia in a murine model

Michael Vansaun, Kyu Lee In, Mary Kay Washington, Lynn Matrisian, David Lee Gorden

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Non-alcoholic fatty liver disease (NAFLD), which includes steatosis and its progression to non-alcoholic steatohepatitis, is a liver disorder of increasing clinical significance. Here we characterize a murine model of high fat diet-induced NAFLD with progression from liver steatosis to histological features compatible with steatohepatitis and more advanced stages of NAFLD in humans, including chronic portal inflammation, pericellular and bridging fibrosis, Mallory body formation, and bile ductular reaction. Chronic changes induced by the prolonged consumption of a high-fat diet alone culminate in the development of primary liver dysplasias. Importantly, we extend these studies to demonstrate that even the early stages of uncomplicated steatosis provide a permissive microenvironment for the growth of colon cancer cells that are metastatic to the liver. High fat diet-induced steatosis, coupled with a splenic injection model of experimental liver metastasis using syngeneic MC38 colon cancer cells, resulted in an increased number of secondary tumor nodules and metastatic burden in steatotic livers. Metastatic nodules were associated with focal peritumoral areas of infiltrating inflammatory cells and associated apoptotic cell populations. These results suggest that the modulation of specific host factors in the steatotic liver contributes to tumor progression in the microenvironment of NAFLD.

Original languageEnglish (US)
Pages (from-to)355-364
Number of pages10
JournalAmerican Journal of Pathology
Volume175
Issue number1
DOIs
StatePublished - Jul 2009
Externally publishedYes

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High Fat Diet
Neoplasm Metastasis
Liver
Fatty Liver
Colonic Neoplasms
Mallory Bodies
Bile
Disease Progression
Neoplasms
Fibrosis
Theoretical Models
Inflammation
Injections
Non-alcoholic Fatty Liver Disease
Growth
Population

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

High fat diet induced hepatic steatosis establishes a permissive microenvironment for colorectal metastases and promotes primary dysplasia in a murine model. / Vansaun, Michael; In, Kyu Lee; Washington, Mary Kay; Matrisian, Lynn; Gorden, David Lee.

In: American Journal of Pathology, Vol. 175, No. 1, 07.2009, p. 355-364.

Research output: Contribution to journalArticle

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