Ablation of in Intestinal Epithelial Cells Causes Intestinal Lipid Accumulation and Reduces NASH in Mice

Overview

Journal Hepatol Commun

Specialty Gastroenterology

Date 2020 Jan 8

PMID 31909358

Citations 7

Authors

Harriet Gaskell

Xiaodong Ge

Romain Desert

Sukanta Das

Hui Han

Daniel Lantvit

Grace Guzman

Natalia Nieto

Affiliations

Soon will be listed here.

Abstract

Nonalcoholic steatohepatitis (NASH) is a metabolic disorder in which poor nutrition and the gut-to-liver interaction play a major role. We previously established that hepatic high mobility group box-1 (HMGB1) is involved in chronic liver disease. HMGB1 increases in patients with NASH and it is expressed in intestinal epithelial cells (IEC); yet, the role of intestinal HMGB1 in the pathogenesis of NASH has not been investigated. Thus, we hypothesized that IEC-derived HMGB1 could play a role in NASH due to local effects in the intestine that govern hepatic steatosis. Control littermates and mice were fed for 1 or 24 weeks a control diet or a high fat, high cholesterol (CHO) and fructose-enriched diet (HFCFD). Hepatic and intestinal injury were analyzed. mice were protected from HFCFD-induced NASH after 1 or 24 weeks of feeding; however, they showed extensive atypical lipid droplet accumulation and increased concentrations of triglycerides (TG) and CHO in jejunal IEC together with lower TG and other lipid classes in serum. Olive oil or CHO gavage resulted in decreased serum TG and CHO in mice, respectively, indicating delayed and/or reduced chylomicron (CM) efflux. There was significant up-regulation of scavenger receptor class B type 1 (SR-B1) and down-regulation of apolipoprotein B48 (ApoB48) proteins, suggesting decreased lipid packaging and/or CM formation that resulted in lesser hepatosteatosis. Ablation of in IEC causes up-regulation of SR-B1 and down-regulation of ApoB48, leads to lipid accumulation in jejunal IEC, decreases CM packaging and/or release, reduces serum TG, and lessens liver steatosis, therefore protecting mice from HFCFD-induced NASH.

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