Effects of SCFAs and TMAO on non-alcoholic fatty liver disease indicating the therapeutic benefits of plant-based diet, and supplemental prebiotics, probiotics and synbiotics

Applied Biological Chemistry

Table 1 Effects of trimethylamine-N-oxide on different states of cholesterol

References	Subject	Treatment	Results
Koeth, Robert A 2013 [29]	Apoe − / − mice	L-carnitin, choline, trimethylamine-N-oxide (TMAO) supplemented diets	↓ Reverse cholesterol transport ↓ Bile acid synthesis and transport ↓ Bile acid pool size ↓ Steatohepatitis ↑ Atherosclerosis ↑ RNA and protein levels in macrophage scavenger receptors involved in cardiovascular disease (CVD) ↑ Macrophage foam cell formation
Zhao, Z. H 2019 [31]	Rats fed high-fat high-cholesterol (HFHC) diet	TMAO (120 mg/kg/day) oral gavage for 8 weeks
Wang, Z 2011 [28]	Apoe − / − mice	Choline (0.5%, 1.0%) or TMAO (0.12%) added in chow diet
Tan, Xuying 2019 [32]	1. Mice fed high-fat diet (HFD) 2. HepG2 cells treated with palmatic acid	1. TMAO (18% w/v) in drinking water for 18 weeks 2. TMAO (at 0.1, 0.2, 0.3, and 0.4 mm) for 24 h	• Correlations between non-alcoholic fatty liver disease (NAFLD) and TMAO, bile acid pool size, and hepatic mRNA cholesterol 7 alpha-hydroxylase (CYP7A1) • Knockdown of CYP7A1 or activation of the farnesoid X receptor (FXR) blocks TMAO-induced lipogenesis ↑ Bile acid synthesis ↑ Proportion of FXR antagonistic species ↑ Lipogenesis and triglyceride (TG) accumulation ↑ Liver dysfunction

CVD cardiovascular disease, CYP7A1 cholesterol 7 alpha-hydroxylase, FXR farnesoid X receptor, HFD high-fat diet, NAFLD non-alcoholic fatty liver disease, TG triglyceride, TMAO trimethylamine-N-oxide, AKT protein kinase B, ALT alanine aminotransferase, AMPK AMP-activated protein kinase, ASC apoptosis-associated speck-like protein, AST aspartate transaminase, BAMBI BMP and activin membrane-bound inhibitor, BMI body mass index, CFU colony-forming unit, CYP7A1 cholesterol 7 alpha-hydroxylase, ERK extracellular signal‐regulated kinase, FXR farnesoid X Receptor, GLP Glucagon-like peptide, HDL-C high-density lipoprotein cholesterol, HFD high-fat diet, IL interleukin, JNK c-Jun N-terminal kinase, LDL low density lipoprotein, LDL-C low-density lipoprotein cholesterol, LGG Lactobacillus rhamnosus GG, LPS lipopolysaccharide, MCD methionine-choline deficient, NAFLD non-alcoholic fatty liver disease, NASH nonalcoholic steatohepatitis, NF-κB Nuclear factor kappa B, NLRP3 NLR family pyrin domain-containing 3, PPAR peroxisome proliferator-activated receptor, SREBP-1c sterol regulatory element binding transcription factor 1 isoform c, TG Triglycerides, TLR toll-like receptor, TNF-α tumor necrosis factor alpha, US ultrasound
A positive or upward effect is denoted by (↑), a negative or downward effect is denoted by (↓)