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Fructose induced endotoxemia in pediatric nonalcoholic Fatty liver disease.

Jin R, Willment A, Patel SS, Sun X, Song M, Mannery YO, Kosters A, McClain CJ, Vos MB - Int J Hepatol (2014)

Bottom Line: In a 24-hour feeding study, endotoxin levels in NAFLD adolescents increased after fructose beverages (consumed with meals) as compared to healthy children.Similarly, endotoxin was significantly increased after adolescents consumed fructose beverages for 2 weeks and remained high although not significantly at 4 weeks.In conclusion, these data provide support for the concept of low level endotoxemia contributing to pediatric NAFLD and the possible role of fructose in this process.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, School of Medicine, Emory University, 2015 Uppergate Drive NE, Atlanta, GA 30322, USA.

ABSTRACT
In preclinical studies of fructose-induced NAFLD, endotoxin appears to play an important role. We retrospectively examined samples from three pediatric cohorts (1) to investigate whether endotoxemia is associated with the presence of hepatic steatosis; (2) to evaluate postprandial endotoxin levels in response to fructose beverage in an acute 24-hour feeding challenge, and (3) to determine the change of fasting endotoxin amounts in a 4-week randomized controlled trial comparing fructose to glucose beverages in NAFLD. We found that adolescents with hepatic steatosis had elevated endotoxin levels compared to obese controls and that the endotoxin level correlated with insulin resistance and several inflammatory cytokines. In a 24-hour feeding study, endotoxin levels in NAFLD adolescents increased after fructose beverages (consumed with meals) as compared to healthy children. Similarly, endotoxin was significantly increased after adolescents consumed fructose beverages for 2 weeks and remained high although not significantly at 4 weeks. In conclusion, these data provide support for the concept of low level endotoxemia contributing to pediatric NAFLD and the possible role of fructose in this process. Further studies are needed to determine if manipulation of the microbiome or other methods of endotoxin reduction would be useful as a therapy for pediatric NAFLD.

No MeSH data available.


Related in: MedlinePlus

Obese adolescents with hepatic steatosis (>5% by MRS) had increased (a) plasma endotoxin levels, (b) plasma TNF-α levels, and (c) plasma MCP-1 levels as compared to obese adolescents without significant steatosis (hepatic fat < 5% by MRS); *P < 0.05.
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Related In: Results  -  Collection


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fig1: Obese adolescents with hepatic steatosis (>5% by MRS) had increased (a) plasma endotoxin levels, (b) plasma TNF-α levels, and (c) plasma MCP-1 levels as compared to obese adolescents without significant steatosis (hepatic fat < 5% by MRS); *P < 0.05.

Mentions: Anthropometrics and laboratory parameters for the 32 obese adolescents with hepatic steatosis and the 11 obese adolescents without hepatic steatosis are reported in Table 1. There were no significant differences in age, gender, body weight, BMI z-score, and hs-CRP between the two groups. Adolescents with hepatic steatosis (>5% by MRS) had increased ALT (P = 0.021), AST (P < 0.001), fasting insulin (P = 0.010), and insulin resistance as assessed by HOMA-IR (P = 0.013) compared with obese control adolescents. The plasma concentration of endotoxin in obese adolescents without hepatic steatosis averaged 1.22 ± 0.30 EU/mL (mean ± SD, ranging from 0.64 to 1.61 EU/mL), while in participants with steatosis, the mean endotoxin level was significantly increased to 1.54 ± 0.52 EU/mL (mean ± SD, ranging from 0.85 to 2.83 EU/mL) (P = 0.019) (Figure 1(a)). In multiple linear regression models, we found that the difference in endotoxin levels between subjects with and without steatosis remained significant after adjusting for BMI z-score (P = 0.036) and for hs-CRP (P = 0.042), respectively, but was blunted after the adjustment for HOMA-IR (P = 0.068) and for the cluster of HOMA-IR, BMI z-score, and hs-CRP (P = 0.056).


Fructose induced endotoxemia in pediatric nonalcoholic Fatty liver disease.

Jin R, Willment A, Patel SS, Sun X, Song M, Mannery YO, Kosters A, McClain CJ, Vos MB - Int J Hepatol (2014)

Obese adolescents with hepatic steatosis (>5% by MRS) had increased (a) plasma endotoxin levels, (b) plasma TNF-α levels, and (c) plasma MCP-1 levels as compared to obese adolescents without significant steatosis (hepatic fat < 5% by MRS); *P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4195259&req=5

fig1: Obese adolescents with hepatic steatosis (>5% by MRS) had increased (a) plasma endotoxin levels, (b) plasma TNF-α levels, and (c) plasma MCP-1 levels as compared to obese adolescents without significant steatosis (hepatic fat < 5% by MRS); *P < 0.05.
Mentions: Anthropometrics and laboratory parameters for the 32 obese adolescents with hepatic steatosis and the 11 obese adolescents without hepatic steatosis are reported in Table 1. There were no significant differences in age, gender, body weight, BMI z-score, and hs-CRP between the two groups. Adolescents with hepatic steatosis (>5% by MRS) had increased ALT (P = 0.021), AST (P < 0.001), fasting insulin (P = 0.010), and insulin resistance as assessed by HOMA-IR (P = 0.013) compared with obese control adolescents. The plasma concentration of endotoxin in obese adolescents without hepatic steatosis averaged 1.22 ± 0.30 EU/mL (mean ± SD, ranging from 0.64 to 1.61 EU/mL), while in participants with steatosis, the mean endotoxin level was significantly increased to 1.54 ± 0.52 EU/mL (mean ± SD, ranging from 0.85 to 2.83 EU/mL) (P = 0.019) (Figure 1(a)). In multiple linear regression models, we found that the difference in endotoxin levels between subjects with and without steatosis remained significant after adjusting for BMI z-score (P = 0.036) and for hs-CRP (P = 0.042), respectively, but was blunted after the adjustment for HOMA-IR (P = 0.068) and for the cluster of HOMA-IR, BMI z-score, and hs-CRP (P = 0.056).

Bottom Line: In a 24-hour feeding study, endotoxin levels in NAFLD adolescents increased after fructose beverages (consumed with meals) as compared to healthy children.Similarly, endotoxin was significantly increased after adolescents consumed fructose beverages for 2 weeks and remained high although not significantly at 4 weeks.In conclusion, these data provide support for the concept of low level endotoxemia contributing to pediatric NAFLD and the possible role of fructose in this process.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, School of Medicine, Emory University, 2015 Uppergate Drive NE, Atlanta, GA 30322, USA.

ABSTRACT
In preclinical studies of fructose-induced NAFLD, endotoxin appears to play an important role. We retrospectively examined samples from three pediatric cohorts (1) to investigate whether endotoxemia is associated with the presence of hepatic steatosis; (2) to evaluate postprandial endotoxin levels in response to fructose beverage in an acute 24-hour feeding challenge, and (3) to determine the change of fasting endotoxin amounts in a 4-week randomized controlled trial comparing fructose to glucose beverages in NAFLD. We found that adolescents with hepatic steatosis had elevated endotoxin levels compared to obese controls and that the endotoxin level correlated with insulin resistance and several inflammatory cytokines. In a 24-hour feeding study, endotoxin levels in NAFLD adolescents increased after fructose beverages (consumed with meals) as compared to healthy children. Similarly, endotoxin was significantly increased after adolescents consumed fructose beverages for 2 weeks and remained high although not significantly at 4 weeks. In conclusion, these data provide support for the concept of low level endotoxemia contributing to pediatric NAFLD and the possible role of fructose in this process. Further studies are needed to determine if manipulation of the microbiome or other methods of endotoxin reduction would be useful as a therapy for pediatric NAFLD.

No MeSH data available.


Related in: MedlinePlus