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Lactoferrin dampens high-fructose corn syrup-induced hepatic manifestations of the metabolic syndrome in a murine model.

Li YC, Hsieh CC - PLoS ONE (2014)

Bottom Line: Our results show that a high-fructose diet stimulates intestinal bacterial overgrowth and increases intestinal permeability, leading to the introduction of endotoxin into blood circulation and liver.The important regulatory roles are played by adipokines including interleukin-1β, interleukin-6, tumor necrosis factor-α, monocyte chemotactic protein-1, and adiponectin, ultimately reducing hepatitis and decreasing serum alanine aminotransferase release.Lactoferrin administration thus significantly lowered liver weight, resulting from a decrease in the triglyceride and cholesterol synthesis that activates hepatic steatosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Animal Science and Biotechnology, Tunghai University, Taichung, Taiwan.

ABSTRACT
Hepatic manifestations of the metabolic syndrome are related obesity, type 2 diabetes/insulin resistance and non-alcoholic fatty liver disease. Here we investigated how the anti-inflammatory properties of lactoferrin can protect against the onset of hepatic manifestations of the metabolic syndrome by using a murine model administered with high-fructose corn syrup. Our results show that a high-fructose diet stimulates intestinal bacterial overgrowth and increases intestinal permeability, leading to the introduction of endotoxin into blood circulation and liver. Immunohistochemical staining of Toll-like receptor-4 and thymic stromal lymphopoietin indicated that lactoferrin can modulate lipopolysaccharide-mediated inflammatory cascade. The important regulatory roles are played by adipokines including interleukin-1β, interleukin-6, tumor necrosis factor-α, monocyte chemotactic protein-1, and adiponectin, ultimately reducing hepatitis and decreasing serum alanine aminotransferase release. These beneficial effects of lactoferrin related to the downregulation of the lipopolysaccharide-induced inflammatory cascade in the liver. Furthermore, lactoferrin reduced serum and hepatic triglycerides to prevent lipid accumulation in the liver, and reduced lipid peroxidation, resulting in 4-hydroxynonenal accumulation. Lactoferrin reduced oral glucose tolerance test and homeostasis model assessment-insulin resistance. Lactoferrin administration thus significantly lowered liver weight, resulting from a decrease in the triglyceride and cholesterol synthesis that activates hepatic steatosis. Taken together, these results suggest that lactoferrin protected against high-fructose corn syrup induced hepatic manifestations of the metabolic syndrome.

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Insulin resistance and OGTT determination in HFCS-induced insulin resistance in the murine model.(A) Blood glucose determined by OGTT after oral administration of glucose (2%). (B) Area under curve (AUC) was calculated for the OGTT. The control group showed a significant increase compared to the naïve group, whereas lactoferrin at 50, 100, and 200 mg/kg markedly reduced the AUC. (C) Fasting serum insulin was determined by ELISA. Insulin levels were significantly increased in the control group compared to the naïve group, and lactoferrin at 50, 100, and 200 mg/kg markedly reduced blood insulin. (D) HOMA-IR insulin resistance calculated from fasting serum glucose and insulin levels. Lactoferrin at 50, 100, and 200 mg/kg markedly reduced blood insulin. Data are presented as mean ± SD (n = 10) and were analyzed using one-way ANOVAs and Duncan's multiple range test. a–d: Different letters indicate significant differences between groups (P<0.05).
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pone-0097341-g003: Insulin resistance and OGTT determination in HFCS-induced insulin resistance in the murine model.(A) Blood glucose determined by OGTT after oral administration of glucose (2%). (B) Area under curve (AUC) was calculated for the OGTT. The control group showed a significant increase compared to the naïve group, whereas lactoferrin at 50, 100, and 200 mg/kg markedly reduced the AUC. (C) Fasting serum insulin was determined by ELISA. Insulin levels were significantly increased in the control group compared to the naïve group, and lactoferrin at 50, 100, and 200 mg/kg markedly reduced blood insulin. (D) HOMA-IR insulin resistance calculated from fasting serum glucose and insulin levels. Lactoferrin at 50, 100, and 200 mg/kg markedly reduced blood insulin. Data are presented as mean ± SD (n = 10) and were analyzed using one-way ANOVAs and Duncan's multiple range test. a–d: Different letters indicate significant differences between groups (P<0.05).

Mentions: The hepatic manifestations of the metabolic syndrome are fatty liver and/or hepatic steatosis linked to insulin resistance. Type 2 diabetes is also a chronic inflammatory condition characterized by elevation of concentrations of ROS and endotoxins. As shown in Figure 3A, measurements of serum glucose by OGTT demonstrated that compared to the naïve group, the control group had higher blood glucose concentrations after fasting and 30, 60, 90, and 120 min after oral glucose administration (Figure 3A; P<0.05). The lactoferrin-treated groups showed significantly lower blood glucose levels at all times compared to the control group. Area under curve (AUC) measurements from the OGTT indicated that glucose levels were significantly higher in the control group than in the naïve group, and that glucose levels were significantly lower in the lactoferrin-treated groups than in the control group (Figure 3B; P<0.05). Fasting insulin levels were significantly reduced in the lactoferrin-treated groups, in a dose-dependent manner (Figure 3C; P<0.05). The homeostatic model assessment (HOMA) is a method used to determine insulin resistance (HOMA-IR). Our data indicate that the lactoferrin-administered groups had significantly reduced HOMA-IR (Figure 3D; P<0.05), suggesting that lactoferrin can lower insulin resistance.


Lactoferrin dampens high-fructose corn syrup-induced hepatic manifestations of the metabolic syndrome in a murine model.

Li YC, Hsieh CC - PLoS ONE (2014)

Insulin resistance and OGTT determination in HFCS-induced insulin resistance in the murine model.(A) Blood glucose determined by OGTT after oral administration of glucose (2%). (B) Area under curve (AUC) was calculated for the OGTT. The control group showed a significant increase compared to the naïve group, whereas lactoferrin at 50, 100, and 200 mg/kg markedly reduced the AUC. (C) Fasting serum insulin was determined by ELISA. Insulin levels were significantly increased in the control group compared to the naïve group, and lactoferrin at 50, 100, and 200 mg/kg markedly reduced blood insulin. (D) HOMA-IR insulin resistance calculated from fasting serum glucose and insulin levels. Lactoferrin at 50, 100, and 200 mg/kg markedly reduced blood insulin. Data are presented as mean ± SD (n = 10) and were analyzed using one-way ANOVAs and Duncan's multiple range test. a–d: Different letters indicate significant differences between groups (P<0.05).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4016362&req=5

pone-0097341-g003: Insulin resistance and OGTT determination in HFCS-induced insulin resistance in the murine model.(A) Blood glucose determined by OGTT after oral administration of glucose (2%). (B) Area under curve (AUC) was calculated for the OGTT. The control group showed a significant increase compared to the naïve group, whereas lactoferrin at 50, 100, and 200 mg/kg markedly reduced the AUC. (C) Fasting serum insulin was determined by ELISA. Insulin levels were significantly increased in the control group compared to the naïve group, and lactoferrin at 50, 100, and 200 mg/kg markedly reduced blood insulin. (D) HOMA-IR insulin resistance calculated from fasting serum glucose and insulin levels. Lactoferrin at 50, 100, and 200 mg/kg markedly reduced blood insulin. Data are presented as mean ± SD (n = 10) and were analyzed using one-way ANOVAs and Duncan's multiple range test. a–d: Different letters indicate significant differences between groups (P<0.05).
Mentions: The hepatic manifestations of the metabolic syndrome are fatty liver and/or hepatic steatosis linked to insulin resistance. Type 2 diabetes is also a chronic inflammatory condition characterized by elevation of concentrations of ROS and endotoxins. As shown in Figure 3A, measurements of serum glucose by OGTT demonstrated that compared to the naïve group, the control group had higher blood glucose concentrations after fasting and 30, 60, 90, and 120 min after oral glucose administration (Figure 3A; P<0.05). The lactoferrin-treated groups showed significantly lower blood glucose levels at all times compared to the control group. Area under curve (AUC) measurements from the OGTT indicated that glucose levels were significantly higher in the control group than in the naïve group, and that glucose levels were significantly lower in the lactoferrin-treated groups than in the control group (Figure 3B; P<0.05). Fasting insulin levels were significantly reduced in the lactoferrin-treated groups, in a dose-dependent manner (Figure 3C; P<0.05). The homeostatic model assessment (HOMA) is a method used to determine insulin resistance (HOMA-IR). Our data indicate that the lactoferrin-administered groups had significantly reduced HOMA-IR (Figure 3D; P<0.05), suggesting that lactoferrin can lower insulin resistance.

Bottom Line: Our results show that a high-fructose diet stimulates intestinal bacterial overgrowth and increases intestinal permeability, leading to the introduction of endotoxin into blood circulation and liver.The important regulatory roles are played by adipokines including interleukin-1β, interleukin-6, tumor necrosis factor-α, monocyte chemotactic protein-1, and adiponectin, ultimately reducing hepatitis and decreasing serum alanine aminotransferase release.Lactoferrin administration thus significantly lowered liver weight, resulting from a decrease in the triglyceride and cholesterol synthesis that activates hepatic steatosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Animal Science and Biotechnology, Tunghai University, Taichung, Taiwan.

ABSTRACT
Hepatic manifestations of the metabolic syndrome are related obesity, type 2 diabetes/insulin resistance and non-alcoholic fatty liver disease. Here we investigated how the anti-inflammatory properties of lactoferrin can protect against the onset of hepatic manifestations of the metabolic syndrome by using a murine model administered with high-fructose corn syrup. Our results show that a high-fructose diet stimulates intestinal bacterial overgrowth and increases intestinal permeability, leading to the introduction of endotoxin into blood circulation and liver. Immunohistochemical staining of Toll-like receptor-4 and thymic stromal lymphopoietin indicated that lactoferrin can modulate lipopolysaccharide-mediated inflammatory cascade. The important regulatory roles are played by adipokines including interleukin-1β, interleukin-6, tumor necrosis factor-α, monocyte chemotactic protein-1, and adiponectin, ultimately reducing hepatitis and decreasing serum alanine aminotransferase release. These beneficial effects of lactoferrin related to the downregulation of the lipopolysaccharide-induced inflammatory cascade in the liver. Furthermore, lactoferrin reduced serum and hepatic triglycerides to prevent lipid accumulation in the liver, and reduced lipid peroxidation, resulting in 4-hydroxynonenal accumulation. Lactoferrin reduced oral glucose tolerance test and homeostasis model assessment-insulin resistance. Lactoferrin administration thus significantly lowered liver weight, resulting from a decrease in the triglyceride and cholesterol synthesis that activates hepatic steatosis. Taken together, these results suggest that lactoferrin protected against high-fructose corn syrup induced hepatic manifestations of the metabolic syndrome.

Show MeSH
Related in: MedlinePlus