Oral Supplementation of Sodium Butyrate Attenuates the Progression of Non-Alcoholic Steatohepatitis

Baumann, Anja; Wei, Huangzhao; Brandt, Annette; Sellmann, Cathrin; Nier, Anika; Burkard, Markus; Venturelli, Sascha; Bergheim, Ina

doi:10.3390/nu12040951

Cited by 31 publications

(49 citation statements)

References 53 publications

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“…Mice in the WD and WD-GP-groups consumed on average 0.3–0.4 g butyric acid /kg BW per day. Oral supplementation of butyrate has been reported to be protective against both NAFLD ( 72 ) and insulin resistance ( 73 ), yet increased levels of butyrate-producing bacteria and levels in feces has also been linked to these diseases ( 23 – 25 , 27 – 29 ). Providing dietary butyric acid in butterfat may have protected mice fed WD and WD-GP against hyperglycemia.…”

Section: Discussionmentioning

confidence: 99%

Grape Polyphenols Attenuate Diet-Induced Obesity and Hepatic Steatosis in Mice in Association With Reduced Butyrate and Increased Markers of Intestinal Carbohydrate Oxidation

Mezhibovsky

Knowles

et al. 2021

Front. Nutr.

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A Western Diet (WD) low in fiber but high in fats and sugars contributes to obesity and non-alcoholic fatty liver disease (NAFLD). Supplementation with grape polyphenols (GPs) rich in B-type proanthocyanidins (PACs) can attenuate symptoms of cardiometabolic disease and alter the gut microbiota and its metabolites. We hypothesized that GP-mediated metabolic improvements would correlate with altered microbial metabolites such as short chain fatty acids (SCFAs). To more closely mimic a WD, C57BL/6J male mice were fed a low-fiber diet high in sucrose and butterfat along with 20% sucrose water to represent sugary beverages. This WD was supplemented with 1% GPs (WD-GP) to investigate the impact of GPs on energy balance, SCFA profile, and intestinal metabolism. Compared to WD-fed mice, the WD-GP group had higher lean mass along with lower fat mass, body weight, and hepatic steatosis despite consuming more calories from sucrose water. Indirect and direct calorimetry revealed that reduced adiposity in GP-supplemented mice was likely due to their greater energy expenditure, which resulted in lower energy efficiency compared to WD-fed mice. GP-supplemented mice had higher abundance of Akkermansia muciniphila, a gut microbe reported to increase energy expenditure. Short chain fatty acid measurements in colon content revealed that GP-supplemented mice had lower concentrations of butyrate, a major energy substrate of the distal intestine, and reduced valerate, a putrefactive SCFA. GP-supplementation also resulted in a lower acetate:propionate ratio suggesting reduced hepatic lipogenesis. Considering the higher sucrose consumption and reduced butyrate levels in GP-supplemented mice, we hypothesized that enterocytes would metabolize glucose and fructose as a replacement energy source. Ileal mRNA levels of glucose transporter-2 (GLUT2, SLC2A2) were increased indicating higher glucose and fructose uptake. Expression of ketohexokinase (KHK) was increased in ileum tissue suggesting increased fructolysis. A GP-induced increase in intestinal carbohydrate oxidation was supported by: (1) increased gene expression of duodenal pyruvate dehydrogenase (PDH), (2) a decreased ratio of lactate dehydrogenase a (LDHa): LDHb in jejunum and colon tissues, and (3) decreased duodenal and colonic lactate concentrations. These data indicate that GPs protect against WD-induced obesity and hepatic steatosis by diminishing portal delivery of lipogenic butyrate and sugars due to their increased intestinal utilization.

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Section: Discussionmentioning

confidence: 99%

Grape Polyphenols Attenuate Diet-Induced Obesity and Hepatic Steatosis in Mice in Association With Reduced Butyrate and Increased Markers of Intestinal Carbohydrate Oxidation

Mezhibovsky

Knowles

et al. 2021

Front. Nutr.

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“…Experimental setup used in the present study and sample size calculations were based on previous studies of our group [25]. Indeed, in these studies, it was shown that in this feeding model, 5 weeks of treatment with a compound/ oil are sufficient to show 'therapeutic´efficacy [25,29]. For the first 8 weeks of the experiment, animals were either fed a liquid control diet (C; 69E% carbohydrates, 12E% fat derived from soybean oil, 19E% protein; Ssniff, Soest, Germany) or a liquid butterfat-, fructose-and cholesterol-rich diet (BFC; 60E% carbohydrates, 25E% fat derived from butterfat, 15E% protein, 50% wt/wt fructose and 0.16% wt/wt cholesterol; Ssniff, Soest, Germany).…”

Section: Animals and Feedingmentioning

confidence: 98%

Exchanging dietary fat source with extra virgin olive oil does not prevent progression of diet-induced non-alcoholic fatty liver disease and insulin resistance

et al. 2020

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Dietary fat is discussed to be critical in the development of non-alcoholic fatty liver disease. Here, we assess the effect of exchanging dietary fat source from butterfat to extra virgin olive oil on the progression of an already existing diet-induced non-alcoholic fatty liver disease in mice. Female C57BL/6J mice were fed a liquid butterfat-, fructose-and cholesterolrich diet (BFC, 25E% from butterfat) or control diet (C, 12%E from soybean oil) for 13 weeks. In week 9, fat sources of some BFC-and C-fed mice were switched either to 25E% or 12E% olive oil (OFC and CO). Glucose and insulin tolerance tests were performed, and markers of liver damage and glucose metabolism were assessed. After 6 weeks of feeding, BFC-fed mice had developed marked signs of insulin resistance, which progressed to week 12 being not affected by the exchange of fat sources. Liver damage was similar between BFC-and OFC-fed mice. Markers of lipid metabolism and lipid peroxidation in liver and of insulin signaling in liver and muscle were also similarly altered in BFC-and OFC-fed mice. Taken together, our data suggest that exchanging butterfat with extra virgin olive oil has no effect on the progression of non-alcoholic fatty liver disease and glucose tolerance in mice.

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“…Overall, supplementation of sodium butyrate has been shown to prevent simple steatosis progression to steatohepatitis through various mechanisms [ 43 ]. Acetate and propionate also have anti-inflammatory effect, however, these two SCFAs can promote lipid accumulation and gluconeogenesis in the liver [ 44 ], therefore, they are unlikely to be used for NAFLD therapy.…”

Section: Gut Microbiota Metabolites In the Pathogenesis Of Nafldmentioning

confidence: 99%

Gut Microbiota Metabolites in NAFLD Pathogenesis and Therapeutic Implications

Chen¹,

Vitetta

2020

IJMS

184

137

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Gut microbiota dysregulation plays a key role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) through its metabolites. Therefore, the restoration of the gut microbiota and supplementation with commensal bacterial metabolites can be of therapeutic benefit against the disease. In this review, we summarize the roles of various bacterial metabolites in the pathogenesis of NAFLD and their therapeutic implications. The gut microbiota dysregulation is a feature of NAFLD, and the signatures of gut microbiota are associated with the severity of the disease through altered bacterial metabolites. Disturbance of bile acid metabolism leads to underactivation of bile acid receptors FXR and TGR5, causal for decreased energy expenditure, increased lipogenesis, increased bile acid synthesis and increased macrophage activity. Decreased production of butyrate results in increased intestinal inflammation, increased gut permeability, endotoxemia and systemic inflammation. Dysregulation of amino acids and choline also contributes to lipid accumulation and to a chronic inflammatory status. In some NAFLD patients, overproduction of ethanol produced by bacteria is responsible for hepatic inflammation. Many approaches including probiotics, prebiotics, synbiotics, faecal microbiome transplantation and a fasting-mimicking diet have been applied to restore the gut microbiota for the improvement of NAFLD.

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Oral Supplementation of Sodium Butyrate Attenuates the Progression of Non-Alcoholic Steatohepatitis

Cited by 31 publications

References 53 publications

Grape Polyphenols Attenuate Diet-Induced Obesity and Hepatic Steatosis in Mice in Association With Reduced Butyrate and Increased Markers of Intestinal Carbohydrate Oxidation

Grape Polyphenols Attenuate Diet-Induced Obesity and Hepatic Steatosis in Mice in Association With Reduced Butyrate and Increased Markers of Intestinal Carbohydrate Oxidation

Exchanging dietary fat source with extra virgin olive oil does not prevent progression of diet-induced non-alcoholic fatty liver disease and insulin resistance

Gut Microbiota Metabolites in NAFLD Pathogenesis and Therapeutic Implications

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