Role of gut microbial metabolites in nonalcoholic fatty liver disease

Zhao, Ze; Lai, Jonathan King-Lam; Qiao, Liang; Fan, Jian Gao

doi:10.1111/1751-2980.12709

Cited by 25 publications

(24 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In line with previous findings, SCFAs have a beneficial influence on hepatic metabolism by preventing the progression of nonalcoholic fatty liver disease (NAFLD), T2DM and insulin resistance (IR) in rodents [21,22] and humans [23,24]. Similarly, studies have demonstrated that SCFAs are key factors in reducing and preventing body weight gain and obesity [25,26].…”

Section: Introductionsupporting

confidence: 83%

Tributyrin Attenuates Metabolic and Inflammatory Changes Associated with Obesity through a GPR109A-Dependent Mechanism

Sato

Yap

Crisma

et al. 2020

Cells

View full text Add to dashboard Cite

Obesity is linked with altered microbial short-chain fatty acids (SCFAs), which are a signature of gut dysbiosis and inflammation. In the present study, we investigated whether tributyrin, a prodrug of the SCFA butyrate, could improve metabolic and inflammatory profiles in diet-induced obese mice. Mice fed a high-fat diet for eight weeks were treated with tributyrin or placebo for another six weeks. We show that obese mice treated with tributyrin had lower body weight gain and an improved insulin responsiveness and glucose metabolism, partly via reduced hepatic triglycerides content. Additionally, tributyrin induced an anti-inflammatory state in the adipose tissue by reduction of Il-1β and Tnf-a and increased Il-10, Tregs cells and M2-macrophages. Moreover, improvement in glucose metabolism and reduction of fat inflammatory states associated with tributyrin treatment were dependent on GPR109A activation. Our results indicate that exogenous targeting of SCFA butyrate attenuates metabolic and inflammatory dysfunction, highlighting a potentially novel approach to tackle obesity.

show abstract

Section: Introductionsupporting

confidence: 83%

Tributyrin Attenuates Metabolic and Inflammatory Changes Associated with Obesity through a GPR109A-Dependent Mechanism

Sato

Yap

Crisma

et al. 2020

Cells

View full text Add to dashboard Cite

show abstract

“…Gut dysbiosis is a hallmark of NAFLD and NASH, in which reduced diversity of gut bacteria is an important characteristic[25,30]. Gut dysbiosis leads to gut bacteria translocation due to the impaired intestinal barrier and increased production of harmful microbial metabolites such as lipopolysaccharide and endogenous ethanol, which contribute to the pathogenesis and progression of NAFLD and NASH[31]. The restoration of the gut microbiota diversity by TMAO may mediate its beneficial role in HFHC diet-induced steatohepatitis.…”

Section: Discussionmentioning

confidence: 99%

Trimethylamine N-oxide attenuates high-fat high-cholesterol diet-induced steatohepatitis by reducing hepatic cholesterol overload in rats

Zhao

Xin

Zhou

et al. 2019

WJG

View full text Add to dashboard Cite

BACKGROUND Trimethylamine N-oxide (TMAO) has been shown to be involved in cardiovascular disease (CVD). However, its role in nonalcoholic steatohepatitis (NASH) is unknown. AIM To determine the effect of TMAO on the progression of NASH. METHODS A rat model was induced by 16-wk high-fat high-cholesterol (HFHC) diet feeding and TMAO was administrated by daily oral gavage for 8 wk. RESULTS Oral TMAO intervention attenuated HFHC diet-induced steatohepatitis in rats. Histological evaluation showed that TMAO treatment significantly alleviated lobular inflammation and hepatocyte ballooning in the livers of rats fed a HFHC diet. Serum levels of alanine aminotransferase and aspartate aminotransferase were also decreased by TMAO treatment. Moreover, hepatic endoplasmic reticulum (ER) stress and cell death were mitigated in HFHC diet-fed TMAO-treated rats. Hepatic and serum levels of cholesterol were both decreased by TMAO treatment in rats fed a HFHC diet. Furthermore, the expression levels of intestinal cholesterol transporters were detected. Interestingly, cholesterol influx-related Niemann-Pick C1-like 1 was downregulated and cholesterol efflux-related ABCG5/8 were upregulated by TMAO treatment in the small intestine. Gut microbiota analysis showed that TMAO could alter the gut microbial profile and restore the diversity of gut flora. CONCLUSION These data suggest that TMAO may modulate the gut microbiota, inhibit intestinal cholesterol absorption, and ameliorate hepatic ER stress and cell death under cholesterol overload, thereby attenuating HFHC diet-induced steatohepatitis in rats. Further studies are needed to evaluate the influence on CVD and define the safe does of TMAO treatment.

show abstract

“…In addition to the liver injury caused by fat accumulation, the perspective of the relationship between intestinal flora and liver disease has become a research focus recently [33,34]. Changes in the composition of intestinal microbial communities and their metabolites can also cause liver damage, such as short-chain fatty acids (SCFA), endogenous ethanol, and bile acids [35]. Therefore, maintaining intestinal flora homeostasis plays an important role in the prevention and treatment of NAFLD.…”

Section: Pharmacological Effects Of Pmr In Nafldmentioning

confidence: 99%

A Candidate Drug for Nonalcoholic Fatty Liver Disease: A Review of Pharmacological Activities of Polygoni Multiflori Radix

Zhou

Liu

et al. 2020

BioMed Research International

View full text Add to dashboard Cite

Nonalcoholic fatty liver disease, a type of metabolic syndrome, continues to rise globally. Currently, there is no approved drug for its treatment. Improving lifestyle and exercise can alleviate symptoms, but patients’ compliance is poor. More and more studies have shown the potential of Polygoni Multiflori Radix (PMR) in the treatment of NAFLD and metabolic syndrome. Therefore, this paper reviews the pharmacological effects of PMR and its main chemical components (tetrahydroxystilbene glucoside, emodin, and resveratrol) on NAFLD. PMR can inhibit the production of fatty acids and promote the decomposition of triglycerides, reduce inflammation, and inhibit the occurrence of liver fibrosis. At the same time, it maintains an oxidation equilibrium status in the body, to achieve the therapeutic purpose of NAFLD and metabolic syndrome. Although more standardized studies and clinical trials are needed to confirm its efficacy, PMR may be a potential drug for the treatment of NAFLD and its complications. However, the occurrence of adverse reactions of PMR has affected its extensive clinical application. Therefore, it is necessary to further study its toxicity mechanism, enhance efficacy and control toxicity, and even reduce toxicity, which will contribute to the safe clinical use of PMR.

show abstract

Role of gut microbial metabolites in nonalcoholic fatty liver disease

Cited by 25 publications

References 83 publications

Tributyrin Attenuates Metabolic and Inflammatory Changes Associated with Obesity through a GPR109A-Dependent Mechanism

Tributyrin Attenuates Metabolic and Inflammatory Changes Associated with Obesity through a GPR109A-Dependent Mechanism

Trimethylamine N-oxide attenuates high-fat high-cholesterol diet-induced steatohepatitis by reducing hepatic cholesterol overload in rats

A Candidate Drug for Nonalcoholic Fatty Liver Disease: A Review of Pharmacological Activities of Polygoni Multiflori Radix

Contact Info

Product

Resources

About