Inhibitory Effects of Sodium Alginate on Hepatic Steatosis in Mice Induced by a Methionine- and Choline-Deficient Diet

Abstract

Nonalcoholic steatohepatitis (NASH) progresses from nonalcoholic fatty liver disease (NAFLD); however, efficacious drugs for NASH treatment are lacking. Sodium alginate (SA), a soluble dietary fiber extracted from brown algae, could protect the small intestine from enterobacterial invasion. NASH pathogenesis has been suggested to be associated with enterobacterial invasion, so we examined the effect of SA on methionine- and choline-deficient (MCD) diet-induced steatohepatitis in mice (the most widely-used model of NASH). The mice (n = 31) were divided into three groups (mice fed with regular chow, MCD diet, and MCD diet premixed with 5% SA) for 4 and 8 weeks. The MCD diet increased lipid accumulation and inflammation in the liver, the NAFLD Activity Score and hepatic mRNA expression of tumor necrosis factor- and collagen 11, and induced macrophage infiltration. Villus shortening, disruption of zonula occludens-1 localization and depletion of mucus production were observed in the small intestine of the MCD-group mice. SA administration improved lipid accumulation and inflammation in the liver, and impaired barrier function in the small intestine. Collectively, these results suggest that SA is useful for NASH treatment because it can prevent hepatic inflammation and fatty degeneration by maintaining intestinal barrier function.

The Edible Brown Seaweed Sargassum horneri (Turner) C. Agardh Ameliorates High-Fat Diet-Induced Obesity, Diabetes, and Hepatic Steatosis in Mice

“…S. horneri extract exerts anti-inflammatory actions in RAW 264.7 macrophage cells through the inhibition of ERK, p -p38, NF-κB, and pro-inflammatory gene expression [ 38 ]. In addition, the anti-inflammatory effects of major components of S. horneri (e.g., fucoidan [ 39 ], alginate [ 40 ], and fucoxanthin [ 41 ]), have also been reported. Thus, supplementation with S. horneri may alleviate inflammation in white adipose tissue, which is partly associated with its anti-obesity effect.…”

Effects of Caffeine and Chlorogenic Acid on Nonalcoholic Steatohepatitis in Mice Induced by Choline-Deficient, L-Amino Acid-Defined, High-Fat Diet

“…Many models of severe inflammation such as the MCD diet model, cholesterol and cholate model, and PTEN null mice do not develop insulin resistance. Nonetheless, they are considered useful for evaluating NASH histopathology and the effects of various substances on NASH [ 50 , 51 , 52 ]. Therefore, the present model is thought to be a robust model for analyzing the histopathology of NASH, but it may not be appropriate for analyzing the pathophysiology of the disease.…”

Effects of Caffeine and Chlorogenic Acid on Nonalcoholic Steatohepatitis in Mice Induced by Choline-Deficient, L-Amino Acid-Defined, High-Fat Diet

“…Many models of severe inflammation such as the MCD diet model, cholesterol and cholate model, and PTEN null mice do not develop insulin resistance. Nonetheless, they are considered useful for evaluating NASH histopathology and the effects of various substances on NASH [50][51][52]. Therefore, the present model is thought to be a robust model for analyzing the histopathology of NASH, but it may not be appropriate for analyzing the pathophysiology of the disease.…”