Metabolomics Characterizes the Effects and Mechanisms of Quercetin in Nonalcoholic Fatty Liver Disease Development

As metabolomics is widely used in the study of disease mechanisms, an increasing number of studies have found that metabolites play an important role in the occurrence of diseases. The aim of this study is to investigate the effects and mechanisms of quercetin in high-fat-sucrose diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) development using nontargeted metabolomics. A rat model of NAFLD was established by feeding with an HFD for 30 and 50 days. The results indicated quercetin exhibited hepatoprotective activity in 30-day HFD-induced NAFLD rats by regulating fatty acid related metabolites (adrenic acid, etc.), inflammation-related metabolites (arachidonic acid, etc.), oxidative stress-related metabolites (2-hydroxybutyric acid) and other differential metabolites (citric acid, etc.). However, quercetin did not improve NAFLD in the 50-day HFD; perhaps quercetin was unable to reverse the inflammation induced by a long-term high-fat diet. These data indicate that dietary quercetin may be beneficial to NAFLD in early stages. Furthermore, combining metabolomics and experimental approaches opens avenues to study the effects and mechanisms of drugs for complex diseases.

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Metabolomics Characterizes the Effects and Mechanisms of Quercetin in the Nonalcoholic Fatty Liver Disease Development

10.20944/preprints201901.0041.v1 ◽

2019 ◽

Author(s):

Yan Xu ◽

Jichun Han ◽

Jinjin Dong ◽

Xiangcheng Fan ◽

Yuanyuan Cai ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Hepatoprotective Activity ◽

High Fat ◽

Nonalcoholic Fatty Liver ◽

Adrenic Acid ◽

Experimental Approaches

As metabolomics is widely used in the study of disease mechanisms, more and more studies have found that metabolites play an important role in the occurrence of diseases. The aim of this study is to investigate the effects and mechanisms of quercetin in high-fat-sucrose diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) development using nontargeted metabolomics. A rat model of NAFLD was established by feeding with a HFD for 30 and 50 days. Results indicated quercetin exhibited hepatoprotective activity in HFD-induced NAFLD rats in 30 days by regulating fatty acids related metabolites (adrenic acid, etc.), inflammation related metabolites (arachidonic acid, etc.), oxidative stress related metabolites (2-hydroxybutyric acid) and other differential metabolites (citric acid, etc.). However, quercetin couldn’t improve NAFLD in 50 days maybe it couldn’t reverse the inflammation condition induced by long-term high-fat diet. These data indicate that dietary quercetin may be beneficial to NAFLD at early stages. Furthermore, combining metabolomics and experimental approaches opens up avenues of effects and mechanisms of drugs for complex diseases.

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Emodin palliates high-fat diet-induced nonalcoholic fatty liver disease in mice via activating the farnesoid X receptor pathway

Journal of Ethnopharmacology ◽

10.1016/j.jep.2021.114340 ◽

2021 ◽

pp. 114340

Author(s):

Chuangpeng Shen ◽

Zhisen Pan ◽

Shuangcheng Wu ◽

Mingxuan Zheng ◽

Chong Zhong ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

High Fat Diet ◽

Fatty Liver Disease ◽

Farnesoid X Receptor ◽

High Fat ◽

Nonalcoholic Fatty Liver

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Long-Term Dietary Potential Renal Acid Load During Adolescence Is Prospectively Associated with Indices of Nonalcoholic Fatty Liver Disease in Young Women

Journal of Nutrition ◽

10.3945/jn.111.150540 ◽

2012 ◽

Vol 142 (2) ◽

pp. 313-319 ◽

Cited By ~ 16

Author(s):

Danika Krupp ◽

Simone A. Johner ◽

Hermann Kalhoff ◽

Anette E. Buyken ◽

Thomas Remer

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Young Women ◽

Fatty Liver Disease ◽

Nonalcoholic Fatty Liver ◽

Potential Renal Acid Load ◽

Acid Load

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Dissociation of hepatic insulin resistance from susceptibility of nonalcoholic fatty liver disease induced by a high-fat and high-carbohydrate diet in mice

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00291.2013 ◽

2014 ◽

Vol 306 (6) ◽

pp. G496-G504 ◽

Cited By ~ 18

Author(s):

Akihiro Asai ◽

Pauline M. Chou ◽

Heng-Fu Bu ◽

Xiao Wang ◽

M. Sambasiva Rao ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Hepatic Steatosis ◽

Fatty Liver Disease ◽

Diet Group ◽

High Fat ◽

Nonalcoholic Fatty Liver ◽

Akt Phosphorylation ◽

High Carbohydrate

Liver steatosis in nonalcoholic fatty liver disease is affected by genetics and diet. It is associated with insulin resistance (IR) in hepatic and peripheral tissues. Here, we aimed to characterize the severity of diet-induced steatosis, obesity, and IR in two phylogenetically distant mouse strains, C57BL/6J and DBA/2J. To this end, mice (male, 8 wk old) were fed a high-fat and high-carbohydrate (HFHC) or control diet for 16 wk followed by the application of a combination of classic physiological, biochemical, and pathological studies to determine obesity and hepatic steatosis. Peripheral IR was characterized by measuring blood glucose level, serum insulin level, homeostasis model assessment of IR, glucose intolerance, insulin intolerance, and AKT phosphorylation in adipose tissues, whereas the level of hepatic IR was determined by measuring insulin-triggered hepatic AKT phosphorylation. We discovered that both C57BL/6J and DBA/2J mice developed obesity to a similar degree without the feature of liver inflammation after being fed an HFHC diet for 16 wk. C57BL/6J mice in the HFHC diet group exhibited severe pan-lobular steatosis, a marked increase in hepatic triglyceride levels, and profound peripheral IR. In contrast, DBA/2J mice in the HFHC diet group developed only a mild degree of pericentrilobular hepatic steatosis that was associated with moderate changes in peripheral IR. Interestingly, both C57BL/6J and DBA/2J developed severe hepatic IR after HFHC diet treatment. Collectively, these data suggest that the severity of diet-induced hepatic steatosis is correlated to the level of peripheral IR, not with the severity of obesity and hepatic IR. Peripheral rather than hepatic IR is a dominant factor of pathophysiology in nonalcoholic fatty liver disease.

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