scholarly journals Modulation of serotonin in the gut-liver neural axis ameliorates the fatty and fibrotic changes in non-alcoholic fatty liver

2021 ◽  
Vol 14 (3) ◽  
pp. dmm048922
Author(s):  
Masayoshi Ko ◽  
Kenya Kamimura ◽  
Takashi Owaki ◽  
Takuro Nagoya ◽  
Norihiro Sakai ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Tight Junction ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Neural Signal ◽  
Alcoholic Fatty Liver ◽  
Serotonin Antagonist ◽  
Neural Axis

ABSTRACTThe etiology of non-alcoholic fatty liver disease (NAFLD) consists of various factors, including neural signal pathways. However, the molecular mechanisms of the autonomic neural signals influencing NAFLD progression have not been elucidated. Therefore, we examined the involvement of the gut-liver neural axis in NAFLD development and tested the therapeutic effect of modulation of this axis in this study. To test the contribution of the gut-liver neural axis, we examined NAFLD progression with respect to body weight, hepatic steatosis, fibrosis, intestinal tight junction, microbiota and short-chain fatty acids in NAFLD models of choline-deficient defined L-amino-acid and high-fat diet-fed mice with or without blockades of autonomic nerves from the liver. Blockade of the neural signal from the liver to the gut in these NAFLD mice models ameliorated the progression of liver weight, hepatic steatosis and fibrosis by modulating serotonin expression in the small intestine. It was related to the severity of the liver pathology, the tight junction protein expression, microbiota diversity and short-chain fatty acids. These effects were reproduced by administrating serotonin antagonist, which ameliorated the NAFLD progression in the NAFLD mice models. Our study demonstrated that the gut-liver neural axis is involved in the etiologies of NAFLD progression and that serotonin expression through this signaling network is the key factor of this axis. Therefore, modulation of the gut-liver neural axis and serotonin antagonist ameliorates fatty and fibrotic changes in non-alcoholic fatty liver, and can be a potential therapeutic target of NAFLD.This article has an associated First Person interview with the first author of the paper.

scholarly journals Excessive Consumption of the Sugar Rich Longan Fruit Promoted the Development of Non-alcoholic Fatty Liver Disease via Mediating Gut Dysbiosis

2021 ◽  
Author(s):  
Huimin Huang ◽  
Mingxing Li ◽  
Yi Wang ◽  
Xiaoxiao Wu ◽  
Qin Wang ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Alcoholic Fatty Liver ◽  
Free Sugars ◽  
Gut Dysbiosis ◽  
Alcoholic Fatty Liver Disease

Abstract Background: Controversy exists as towards the association of excessive fruits intake and certain disease risks. Longan is an edible fruit rich in high levels of fructose, glucose and sucrose. The aim of this study was to provide direct evidence on the effect of the sugar rich longan fruit on the development of non-alcoholic fatty liver disease (NAFLD). Chemical profiling of longan fruit was conducted using LC-HRMS and HPLC-ELSD.Results: Longan extracts at the doses of 4.0 g/kg, 8.0 and 16.0 g/kg were orally administered for 4 weeks to healthy C57BL/6J mice or to C57BL/6J mice fed with a HFD diet. Fecal microbiome was analyzed by 16S rRNA sequencing. The amounts of short chain fatty acids (SCFAs) in colonic contents were determined by GC-MS. Colon and liver tissues were used for histopathological examination after H&E, Masson’s trichrome, and Oil-red O staining. ELISA method was used for biochemical analysis in serum. In mice fed a normal diet, repeated longan intake for 4 weeks at excess doses (8 or 16 g/kg), but not the normal dose (4 g/kg), promoted inflammation and gut dysbiosis-like status and reduced short-chain fatty acids (SCFAs) production. In high-fat diet (HFD)-fed mice, longan intake at 4 g/kg hardly influenced the NAFLD development. In contrast, excess longan intake (8 or 16 g/kg) promoted NAFLD pathogenesis, including increased abnormality in hepatic indices, elevated inflammation, and gut permeability associated with more severe liver steatosis and fibrosis. Moreover, the exacerbated pathogenic markers were positively correlated with increased blood sugar, aggravated HFD-associated microbial dysbiosis. Conclusions: Effects mediated by excess longan intake resembled that of equivalent free sugars supplementation, suggesting that high level of free sugars in fruits contributed to the promotion of NAFLD development as demonstrated in case of excessive longan intake.

scholarly journals Use of Short-Chain Fatty Acids for the Recovery of the Intestinal Epithelial Barrier Affected by Bacterial Toxins

2021 ◽  
Vol 12 ◽  
Author(s):  
Diliana Pérez-Reytor ◽  
Carlos Puebla ◽  
Eduardo Karahanian ◽  
Katherine García
Keyword(s):  
Fatty Acids ◽  
Tight Junction ◽  
Intestinal Barrier ◽  
Short Chain Fatty Acids ◽  
Enteric Pathogens ◽  
Short Chain ◽  
Intestinal Lumen ◽  
Barrier Integrity ◽  
Intestinal Barrier Integrity ◽  
Chain Fatty Acids

Short-chain fatty acids (SCFAs) are carboxylic acids produced as a result of gut microbial anaerobic fermentation. They activate signaling cascades, acting as ligands of G-protein-coupled receptors, such as GPR41, GPR43, and GPR109A, that can modulate the inflammatory response and increase the intestinal barrier integrity by enhancing the tight junction proteins functions. These junctions, located in the most apical zone of epithelial cells, control the diffusion of ions, macromolecules, and the entry of microorganisms from the intestinal lumen into the tissues. In this sense, several enteric pathogens secrete diverse toxins that interrupt tight junction impermeability, allowing them to invade the intestinal tissue and to favor gastrointestinal colonization. It has been recently demonstrated that SCFAs inhibit the virulence of different enteric pathogens and have protective effects against bacterial colonization. Here, we present an overview of SCFAs production by gut microbiota and their effects on the recovery of intestinal barrier integrity during infections by microorganisms that affect tight junctions. These properties make them excellent candidates in the treatment of infectious diseases that cause damage to the intestinal epithelium.

Jaboticaba berry peel intake increases short chain fatty acids production and prevent hepatic steatosis in mice fed high-fat diet

2018 ◽  
Vol 48 ◽  
pp. 266-274 ◽  
Author(s):  
Ângela Giovana Batista ◽  
Juliana Kelly da Silva-Maia ◽  
Monique Culturato P. Mendonça ◽  
Edilene Siqueira Soares ◽  
Glaucia Carielo Lima ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
High Fat ◽  
Chain Fatty Acids

Microbiota fermentation characteristics of acylated starches and regulation mechanism of short-chain fatty acids on hepatic steatosis

2021 ◽  
Author(s):  
Mei Li ◽  
Jing Wang ◽  
Fenfen Wang ◽  
Padraig Strappe ◽  
Wenting Liu ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Lipid Metabolism ◽  
Hepatic Steatosis ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Regulation Mechanism ◽  
Chain Fatty Acids

Starches acylated with specific short-chain fatty acids (SCFAs) have the potential to provide specificity in SCFA delivery. It is well documented that SCFAs are involved in lipid metabolism, but the...

Increase in long-chain polyunsaturated fatty acid n−6/n−3 ratio in relation to hepatic steatosis in patients with non-alcoholic fatty liver disease

2004 ◽  
Vol 106 (6) ◽  
pp. 635-643 ◽  
Author(s):  
Julia ARAYA ◽  
Ramón RODRIGO ◽  
Luis A. VIDELA ◽  
Lilian THIELEMANN ◽  
Myriam ORELLANA ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Liver Disease ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease ◽  
Long Chain

Hepatic steatosis is a major feature associated with NAFLD (non-alcoholic fatty liver disease). The aims of the present study were to assess the levels of PUFA (polyunsaturated fatty acids) in liver total lipids, triacylglycerols (triglycerides) and phospholipids of NAFLD patients in relation to those in adipose tissue and hepatic indexes related to oxidative stress as factors contributing to hepatic steatosis. Eleven control subjects and 19 patients with NAFLD were studied. Analysis of liver and abdominal adipose tissue fatty acids was carried out by GLC. The liver content of protein carbonyl groups and malondialdehyde were taken as indexes related to oxidative stress. NAFLD patients had a depletion in LCPUFA (long-chain PUFA) of the n-6 and n-3 series in liver triacylglycerols, with decreased 20:4,n-6/18:2,n-6 and (20:5,n-3+22:6,n-3)/18:3,n-3 ratios, whereas liver phospholipids contained higher n-6 and lower n-3 LCPUFA. These findings were accompanied by an enhancement of (i) n-6/n-3 ratio in liver and adipose tissue, (ii) 18:1,n-9 trans levels in adipose tissue, and (iii) hepatic lipid peroxidation and protein oxidation indexes. It is concluded that a marked enhancement in LCPUFA n-6/n-3 ratio occurs in the liver of NAFLD patients, a condition that may favour lipid synthesis over oxidation and secretion, thereby leading to steatosis. Depletion of hepatic LCPUFA may result from both defective desaturation of PUFA, due to inadequate intake of precursors, such as 18:3,n-3, and higher intake of the 18:1,n-9 trans isomer leading to desaturase inhibition, and from an increased peroxidation of LCPUFA due to oxidative stress.

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