Fructose Induced Endotoxemia in Pediatric Nonalcoholic Fatty Liver Disease

Jin, Ran; Willment, Andrew; Patel, Shivani; Sun, Xiaoyan; Song, Ming; Mannery, Yanci O.; Kosters, Astrid; McClain, Craig J.; Vos, Miriam B.

doi:10.1155/2014/560620

Cited by 82 publications

(65 citation statements)

References 34 publications

(42 reference statements)

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“…Consistent with the animal models, several recent studies have reported elevated levels of blood endotoxin in adult patients with simple steatosis and NASH [38, 39], as well as in children with NAFLD [40, 41]. Intestinal permeability was correlated with the liver disease severity; specifically, intestinal permeability was increased in children with steatohepatitis compared to those with steatosis only [42].…”

Section: Nafld: Gut Barrier Endotoxemia and Dietary Factorsmentioning

confidence: 68%

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

Kirpich

Marsano

McClain

2015

Clinical Biochemistry

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255

176

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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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Section: Nafld: Gut Barrier Endotoxemia and Dietary Factorsmentioning

confidence: 68%

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

Kirpich

Marsano

McClain

2015

Clinical Biochemistry

Self Cite

255

176

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“…Indeed, the administration of antibiotics to reduce the endotoxemia can improve the fatty liver (88, 89). Endotoxemia has also been shown to be elevated in children with NAFLD (91). Thus, the microbiome may have a role in fructose-induced fatty liver through an interaction with fructose metabolism in the intestinal wall.…”

Section: Fructokinase the Principal Enzyme Driving Fructose-induced mentioning

confidence: 99%

Fructose and sugar: A major mediator of non-alcoholic fatty liver disease

Jensen

Abdelmalek

Sullivan

et al. 2018

Journal of Hepatology

685

490

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Nonalcoholic Fatty Liver Disease (NAFLD) is the hepatic manifestation of metabolic syndrome, and its rising prevalence parallels the rise in obesity and diabetes. Historically thought to result from overnutrition and sedentary lifestyle, recent evidence suggests that diets high in sugar (from sucrose and/or high fructose corn syrup (HFCS)) not only increases the risk for NAFLD, but also, nonalcoholic steatohepatitis (NASH). Here we review the experimental and clinical evidence that fructose precipitates fat accumulation in the liver, due to both increased lipogenesis and impaired fat oxidation. Recent evidence suggests that the predisposition to fatty liver is linked with metabolism of fructose by fructokinase C, resulting in ATP consumption, nucleotide turnover and uric acid generation that mediate fat accumulation. Alterations in gut permeability, microbiome, and associated endotoxemia contributes to the risk of NAFLD and NASH. Early clinical studies suggest that reducing sugary beverages and total fructose intake, especially from added sugars, may have a significant benefit on reducing hepatic fat accumulation. We suggest larger, more definitive trials to determine if lowering sugar/HFCS intake, and/or blocking uric acid generation, may help reduce NAFLD and its downstream complications of cirrhosis and chronic liver disease.

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“…Gut wall integrity and the intestinal microbiome are impaired by high-fat and high-sugar diets commonly consumed by the obese (106)(107)(108). Evidence points to the importance of fiber, its metabolites, and other dietary components (106,(109)(110)(111) in maintaining a healthy gut barrier (112,113) and intestinal microbiome (114) to prevent diet-induced chronic inflammation and insulin resistance (84,106,115).…”

Section: Gut Wall Integritymentioning

confidence: 99%

A multicomponent nutrient bar promotes weight loss and improves dyslipidemia and insulin resistance in the overweight/obese: chronic inflammation blunts these improvements

McCann¹,

Shigenaga²,

Mietus‐Snyder³

et al. 2015

The FASEB Journal

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This study determined if twice-daily consumption of a nutrient-dense bar intended to fill gaps in Western diets, without other dietary/lifestyle requirements, favorably shifted metabolic/anthropometric indicators of dysregulation in a healthy direction. Three 8-wk clinical trials in 43 healthy lean and overweight/obese (OW/OB) adults, who served as their own controls, were pooled for analysis. In less inflamed OW/OB [highsensitivity C-reactive protein (hsCRP) <1.5], statistically significant decreases occurred in weight (21.1 6 0.5 kg), waist circumference (23.1 6 1.4 cm), diastolic blood pressure (24.1 6 1.6 mmHg), heart rate [HR; 24.0 6 1.7 beats per minute (bpm)], triglycerides (272 6 38.2 mg/dl), insulin resistance (homeostatic model of insulin resistance) (20.72 6 0.3), and insulin (22.8 6 1.3 mU/L); an increase in HDL-2b (+303 6 116 nM) and realignment of LDL lipid subfractions toward a less atherogenic profile [decreased small LDL IIIb (244 6 23.5 nM), LDL IIIa (299 6 43.7 nM), and increased large LDL I (+66 6 28.0 nM)]. In the more inflamed OW/OB (hsCRP >1.5), inflammation was reduced at 2 wk (20.66 mg/L), and HR at 8 wk (23.4 6 1.3 bpm). The large HDL subfraction (10.5-14.5 nm) increased at 8 wk (+346 6 126 nM). Metabolic improvements were also observed in lean participants. Thus, favorable changes in measures of cardiovascular health, insulin resistance, inflammation, and obesity were initiated within 8 wk in the OW/OB by replacing deficiencies in Western diets without requiring other dietary or lifestyle modifications; chronic inflammation blunted most improvements. , fiber, and plant polyphenolics (1-4), is a major cause of the increasing prevalence of obesity worldwide (5-7). Such diets directly contribute to the metabolic dysregulation that usually accompanies obesity (8)(9)(10)(11) and is also present in ;25% of lean individuals (12, 13). Metabolic dysregulation includes chronic inflammation, insulin resistance, dyslipidemia, and oxidative stress (14, 15). Several metabolic abnormalities, together with visceral adiposity and high blood pressure (BP), are collectively termed "the metabolic syndrome" (11, 16). Various aspects of metabolic dysregulation have been shown to be independent risk factors for cardiovascular disease (CVD) and type 2 diabetes, and putative risk factors for the many other obesityassociated diseases including cancer, autoimmune disorders, asthma, and neurodegenerative conditions (17)(18)(19)(20)(21)(22).Because poor diets are a root cause of these health problems, an obvious approach to the obesity epidemic would be to improve dietary habits. However, changing dietary patterns is difficult for many people to initiate and sustain (23-25).Abbreviations: aka, also known as; BMI, body mass index; BP, blood pressure; bpm, beats per minute; CVD, cardiovascular disease; DBP, diastolic blood pressure; DHA, docosahexaenoic acid; HDL-L, large HDL subfraction; HDLPs, total HDL subfractions; HOMA-IR, homeostatic model of insulin resistance; HPMC, hydroxypropylmethylcellulose; HR, ...

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Fructose Induced Endotoxemia in Pediatric Nonalcoholic Fatty Liver Disease

Cited by 82 publications

References 34 publications

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

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

Fructose and sugar: A major mediator of non-alcoholic fatty liver disease

A multicomponent nutrient bar promotes weight loss and improves dyslipidemia and insulin resistance in the overweight/obese: chronic inflammation blunts these improvements

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