Toll‐like receptor‐4 signalling in the progression of non‐alcoholic fatty liver disease induced by high‐fat and high‐fructose diet in mice

Liu, Jing; Zhuang, Zhenjie; Bian, Dongxue; Ma, Xiaojie; Xun, Yunhao; Yang, Wenjun; Luo, Yan; Liu, Yinlan; Jia, Ling; Wang, Yan; Zhu, Mingli; Ye, De-wei; Zhou, Gang; Lou, Guo-qiang; Shi, Junping

doi:10.1111/1440-1681.12241

Cited by 64 publications

(43 citation statements)

References 29 publications

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“…Fructose-induced endotoxemia activates Kupffer cells via upregulating TLR4/MyD88, which may be partially involved in the development of NAFLD [170], and subsequently trigger NF-κB activation and TNF-α overproduction [178]. Hepatic steatosis and inflammation are significantly ameliorated in TLR4-mutant mice compared with TLR4-WT mice [179]. Knock-out of lipopolysaccharide-binding protein (LBP) partially protects mice from fructose-induced NAFLD by blocking endotoxin from binding to TLR4 in liver [180].…”

Section: Indirect Dangerous Factors In Tissue and Organ Dysfunctiomentioning

confidence: 99%

High Dietary Fructose: Direct or Indirect Dangerous Factors Disturbing Tissue and Organ Functions

2017

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High dietary fructose is a major contributor to insulin resistance and metabolic syndrome, disturbing tissue and organ functions. Fructose is mainly absorbed into systemic circulation by glucose transporter 2 (GLUT2) and GLUT5, and metabolized in liver to produce glucose, lactate, triglyceride (TG), free fatty acid (FFA), uric acid (UA) and methylglyoxal (MG). Its extrahepatic absorption and metabolism also take place. High levels of these metabolites are the direct dangerous factors. During fructose metabolism, ATP depletion occurs and induces oxidative stress and inflammatory response, disturbing functions of local tissues and organs to overproduce inflammatory cytokine, adiponectin, leptin and endotoxin, which act as indirect dangerous factors. Fructose and its metabolites directly and/or indirectly cause oxidative stress, chronic inflammation, endothelial dysfunction, autophagy and increased intestinal permeability, and then further aggravate the metabolic syndrome with tissue and organ dysfunctions. Therefore, this review addresses fructose-induced metabolic syndrome, and the disturbance effects of direct and/or indirect dangerous factors on the functions of liver, adipose, pancreas islet, skeletal muscle, kidney, heart, brain and small intestine. It is important to find the potential correlations between direct and/or indirect risk factors and healthy problems under excess dietary fructose consumption.

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Section: Indirect Dangerous Factors In Tissue and Organ Dysfunctiomentioning

confidence: 99%

High Dietary Fructose: Direct or Indirect Dangerous Factors Disturbing Tissue and Organ Functions

2017

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“…Another study reported that fructose-induced NAFLD is associated with intestinal bacterial overgrowth and increased intestinal permeability leading to an endotoxin-dependent activation of hepatic Kupffer cells and liver injury in mice [34]. Inactivation of TLR4, a receptor for LPS [34, 35], as well as administration of prebiotics and probiotics to modulate gut microbiota [36, 37] ameliorate fructose-induced hepatic steatosis in rodents.…”

Section: Nafld: Gut Barrier Endotoxemia and Dietary Factorsmentioning

confidence: 99%

Gut–liver axis, nutrition, and non-alcoholic fatty liver disease

Kirpich

Marsano

McClain

2015

Clinical Biochemistry

245

167

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Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of diseases involving hepatic fat accumulation, inflammation with the potential progression to fibrosis and cirrhosis over time. NAFLD is often associated with obesity, insulin resistance, and diabetes. The interactions between the liver and the gut, the so-called ”gut-liver axis”, play a critical role in NAFLD onset and progression. Compelling evidence links the gut microbiome, intestinal barrier integrity, and NAFLD. The dietary factors may alter the gut microbiota and intestinal barrier function, favoring the occurrence of metabolic endotoxemia and low grade inflammation, thereby contributing to the development of obesity and obesity-associated fatty liver disease. Therapeutic manipulations with prebiotics and probiotics to modulate the gut microbiota and maintain intestinal barrier integrity are potential agents for NAFLD management. This review summarizes the current knowledge regarding the complex interplay between the gut microbiota, intestinal barrier, and dietary factors in NAFLD pathogenesis. The concepts addressed in this review have important clinical implications, although more work needs to be done to understand how dietary factors affect the gut barrier and microbiota, and to comprehend how microbe-derived components may interfere with the host’s metabolism contributing to NAFLD development.

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“…TLR-4 is an important component of the innate immune system signaling through different ligands that recognize, among others, LPS, associated with kidney disease [7,8]. Saturated fatty acids [8], fructose [9,10], or sucrose can activate inflammatory pathways observed in obesity and kidney injury [7,8]. LPS, in turn, induces insulin resistance through the activation of the transcription factor NF-κB (nuclear factor kappa-beta) which promotes the expression of inflammatory cytokines [4], such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), which contribute to the impairment of insulin signaling, affecting kidney function [11].…”

Section: Introductionmentioning

confidence: 99%

Differential Effect of Sucrose and Fructose in Combination with a High Fat Diet on Intestinal Microbiota and Kidney Oxidative Stress

et al. 2017

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There is controversial information about the adverse effect of sucrose (S) or fructose (F) in the development of obesity. Thus, the purpose of the study was to evaluate the effect of S or F in a high fat diet (HF) on gut microbiota and renal oxidative stress. Rats were fed for four months with either high-fat + sucrose (HFS) or high-fat + fructose (HFF) or a control diet (C). Half of the HFS or HFF groups were maintained with the same diet and the other half were switched to the consumption of C. HFS and HFF groups increased 51% and 19% body weight, respectively, compared with the C group. Body fat mass, metabolic inflexibility, glucose intolerance, lipopolysaccharide (LPS), insulin, renal reactive oxygen species (ROS), malondialdehyde (MDA), Nadphox, and Srebp-1 were significantly higher and antioxidant enzymes and lean body mass were significantly lower in the HFS group with respect to the HF-F group. Change in the consumption of HFS or HFF to a C diet ameliorated the insulin and glucose intolerance. The type of carbohydrate differentially modified the microbiota composition, however, both groups significantly decreased C. eutactus with respect to the C group. Thus, metabolic alterations with the HFS diet had a more detrimental effect than HFF.

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Toll‐like receptor‐4 signalling in the progression of non‐alcoholic fatty liver disease induced by high‐fat and high‐fructose diet in mice

Cited by 64 publications

References 29 publications

High Dietary Fructose: Direct or Indirect Dangerous Factors Disturbing Tissue and Organ Functions

High Dietary Fructose: Direct or Indirect Dangerous Factors Disturbing Tissue and Organ Functions

Gut–liver axis, nutrition, and non-alcoholic fatty liver disease

Differential Effect of Sucrose and Fructose in Combination with a High Fat Diet on Intestinal Microbiota and Kidney Oxidative Stress

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