Treatment with alpha‐galactosylceramide protects mice from early onset of nonalcoholic steatohepatitis: Role of intestinal barrier function

Engstler, Anna Janina; Sellmann, Cathrin; Wei, Huangzhao; Brandt, Annette; Herz, Kathleen; Priebs, Josephine; Bergheim, Ina

doi:10.1002/mnfr.201600985

Cited by 11 publications

(6 citation statements)

References 48 publications

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“…Caloric intake of FFC-fed groups per se was significantly higher than in C-fed groups while body weight gain between C- and FFC-fed mice was similar regardless of additional treatments. Despite not developing overweight or obesity and in line with previous findings using similar kind of feeding model [29], [34], [36], FFC-fed mice developed early signs of NASH with massive macrovesicular fat accumulation and marked inflammatory alterations after 6 weeks (see Fig. 1, Table 1).…”

Section: Resultssupporting

confidence: 90%

“…All experiments were performed under controlled conditions and mice had free access to tap water at all times. Long-term experiments : Mice were adapted to a liquid control diet (C; 69E% carbohydrates, 12E% fat, 19E% protein; Ssniff, Soest, Germany) for 10 days as detailed previously [29]. Animals (n = 6/ group) were then randomly assigned to the following groups: mice fed a fat-, fructose- and cholesterol-rich diet (FFC; 60E% carbohydrates, 25E% fat, 15E% protein with 50% wt/wt fructose and 0.16% wt/wt cholesterol; Ssniff, Soest, Germany), mice fed a FFC diet enriched with commercially available freeze-dried decaffeinated coffee purchased in a local store (FFC+DeCaf, 6 g/kg BW), mice fed C diet or mice fed C diet enriched with the decaffeinated coffee (C+DeCaf, 6 g/kg BW).…”

Section: Methodsmentioning

confidence: 99%

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Consumption of decaffeinated coffee protects against the development of early non-alcoholic steatohepatitis: Role of intestinal barrier function

et al. 2019

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BackgroundNon-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide lacking universally accepted therapies. Studies suggest that coffee consumption is associated with a reduced risk of NAFLD; however, molecular mechanisms and ingredients involved remain to be fully understood. Here, we determined the effects of regular intake of decaffeinated coffee on the development of NAFLD in mice, and molecular mechanisms involved.MethodsFemale C57BL/6J mice (n = 6–7/ group) were pair-fed either a liquid control diet (C) or fat-, fructose- and cholesterol-rich diet (FFC) +/- decaffeinated coffee (DeCaf, 6 g/kg BW) for 4 days or 6 weeks. Indices of liver damage, hepatic inflammation and parameters of insulin resistance and intestinal permeability as well as nitric oxide system were determined.ResultsEarly signs of insulin resistance and non-alcoholic steatohepatitis (NASH) found after 6 weeks of FFC feeding were significantly lower in FFC+DeCaf-fed mice when compared to FFC-fed animals. Moreover, elevation of portal endotoxin levels and loss of tight junction proteins in proximal small intestine found in FFC-fed mice were significantly attenuated in FFC+DeCaf-fed animals. These beneficial effects of DeCaf were associated with a protection against the significant induction of inducible NO-synthase protein levels and 3-nitrotyrosine protein adducts found in proximal small intestine of FFC-fed mice. Similar protective effects of DeCaf were also found in mice fed the FFC diet short-term.ConclusionOur results suggest that protective effects of DeCaf on the development of NAFLD are at least in part related to maintaining intestinal barrier function.

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Section: Resultssupporting

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Consumption of decaffeinated coffee protects against the development of early non-alcoholic steatohepatitis: Role of intestinal barrier function

et al. 2019

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“…To determine protein levels of occludin and β-actin in proximal small intestine, protein lysates were obtained using Trizol (peqGOLD Trifast; Darmstadt, Germany) as previously described [ 30 ]. Protein lysates (1 µg/µL for occludin and 0.1 µg/µL for β-actin) were separated in a sodium dodecyl sulfate–polyacrylamide gel and transferred to a Hybond TM -P polyvinylidene difluoride membrane (Bio-Rad Laboratories, USA).…”

Section: Methodsmentioning

confidence: 99%

Fortifying Butterfat with Soybean Oil Attenuates the Onset of Diet-Induced Non-Alcoholic Steatohepatitis and Glucose Intolerance

et al. 2021

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The addition of plant oils such as soybean oil (S) to a diet rich in saturated fatty acids is discussed as a possible route to prevent or diminish the development of metabolic disease. Here, we assessed whether a butterfat-rich diet fortified with S affects the development of early non-alcoholic steatohepatitis (NASH) and glucose intolerance. Female C57BL/6J mice were fed a standard-control diet (C); a fat-, fructose-, and cholesterol-rich diet (FFC, 25E% butterfat, 50% (wt./wt.) fructose, 0.16% (wt./wt.) cholesterol); or FFC supplemented with S (FFC + S, 21E% butterfat + 4E% S) for 13 weeks. Indicators of liver damage, inflammation, intestinal barrier function, and glucose metabolism were measured. Lipopolysaccharide (LPS)-challenged J774A.1 cells were incubated with linolenic and linoleic acids (ratio 1:7.1, equivalent to S). The development of early NASH and glucose intolerance was significantly attenuated in FFC + S–fed mice compared to FFC-fed mice associated with lower hepatic toll-like receptor-4 mRNA expression, while markers of intestinal barrier function were significantly higher than in C-fed mice. Linolenic and linoleic acid significantly attenuated LPS-induced formation of reactive nitrogen species and interleukin-1 beta mRNA expression in J774A.1 cells. Our results indicate that fortifying butterfat with S may attenuate the development of NASH and glucose intolerance in mice.

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“…diets rich in fat, fructose and/ or cholesterol). 20,28,[55][56][57][58][59][60][61][62] Furthermore, targeting intestinal microbiota for example, through treating animals with a mix of antibiotics targeting Gram-positive and Gramnegative bacteria while feeding them a MASLD-inducing diet thereby reducing prevalence of bacteria >90%-95%, has repeatedly been shown to be related with a marked dampening of the development of MASLD. 49,63,64 This was also associated with a diminished TLR-response and activation of downstream signalling cascades in the liver.…”

Section: Intestinal Barrier Dysfunction and Bacterial Endotoxin In Th...mentioning

confidence: 99%

The relevance of intestinal barrier dysfunction, antimicrobial proteins and bacterial endotoxin in metabolic dysfunction‐associated steatotic liver disease

Bergheim,

Moreno‐Navarrete

2024

Eur J Clin Investigation

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BackgroundMetabolic dysfunction‐associated steatotic liver disease (MASLD) is a leading cause of end‐stage liver disease associated with increased mortality and cardiovascular disease. Obesity and diabetes are the most important risk factors of MASLD. It is well‐established that obesity‐associated insulin resistance leads to a situation of tissue lipotoxicity characterized by an accumulation of excess fat in non‐fat tissues such as the liver, promoting the development of MASLD, and its progression into metabolic dysfunction‐associated steatohepatitis.MethodsHere, we aimed to review the impact of disrupted intestinal permeability, antimicrobial proteins and bacterial endotoxin in the development and progression of MASLD.Results and ConclusionRecent studies demonstrated that obesity‐ and obesogenic diets‐associated alterations of intestinal microbiota along with the disruption of intestinal barrier integrity, the alteration in antimicrobial proteins and, in consequence, an enhanced translocation of bacterial endotoxin into bloodstream might contribute to this pathological process through to impacting liver metabolism and inflammation.

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Treatment with alpha‐galactosylceramide protects mice from early onset of nonalcoholic steatohepatitis: Role of intestinal barrier function

Abstract: Taken together, our data suggest that the protective effects of αGalCer against the development of a diet-induced NASH in mice are associated with a protection against the increased translocation of intestinal bacterial endotoxins associated with the development of NASH.

Cited by 11 publications

References 48 publications

Consumption of decaffeinated coffee protects against the development of early non-alcoholic steatohepatitis: Role of intestinal barrier function

Consumption of decaffeinated coffee protects against the development of early non-alcoholic steatohepatitis: Role of intestinal barrier function

Fortifying Butterfat with Soybean Oil Attenuates the Onset of Diet-Induced Non-Alcoholic Steatohepatitis and Glucose Intolerance

The relevance of intestinal barrier dysfunction, antimicrobial proteins and bacterial endotoxin in metabolic dysfunction‐associated steatotic liver disease

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