Endocrinology. 2004 Feb;145(2):548-55. Epub 2003 Oct 23. Related
Articles, Links
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High dietary fructose induces a hepatic stress response resulting in
cholesterol and lipid dysregulation.
Kelley GL, Allan G, Azhar S.
Insmed Incorporated, 4851 Lake Brook Drive, Glen Allen, VA 23058,
USA.
High-fructose feeding causes diet-induced alterations of lipid
metabolism and decreased insulin sensitivity with alterations of hepatic
pyruvate dehydrogenase and hepatic very low-density lipoprotein
secretion. Inflammatory cytokines also induce dramatic changes in lipid
metabolism, particularly in serum triglycerides via increased hepatic
secretion and/or delayed clearance of very low-density lipoprotein. The
aim of this study was to determine whether the mechanism of lipid
dysregulation in the high-fructose diet is induced by stress response
pathways. Animals were fed a high-fructose diet for 14 d to establish
hypertriglyceridemia and then were treated with lipoxygenase inhibitors
for 4 d concurrent with the diet. At the end of drug treatment, the
animals were divided into two groups and treated with lipopolysaccharide
or a vehicle. Serum samples were taken pretreatment and posttreatment,
and liver tissue was harvested at the end of study. Serum samples were
tested for metabolic parameters, and the tissue samples were tested for
metabolic and stress pathway responses. Our results show that
fructose-fed rats have changes in the c-Jun N-terminal kinase pathway
with correspondingly elevated activator protein-1 activity, consistent
with an inflammatory response. Treatment with lipoxygenase inhibitors
reversed the hypertriglyceridemia and also reduced activator protein-1
activation, suggesting that the basis for lipid dysregulation in this
model is due to activation of inflammatory pathways in the liver.
PMID: 14576175 [PubMed - in process]
Articles, Links
Click here to read
High dietary fructose induces a hepatic stress response resulting in
cholesterol and lipid dysregulation.
Kelley GL, Allan G, Azhar S.
Insmed Incorporated, 4851 Lake Brook Drive, Glen Allen, VA 23058,
USA.
High-fructose feeding causes diet-induced alterations of lipid
metabolism and decreased insulin sensitivity with alterations of hepatic
pyruvate dehydrogenase and hepatic very low-density lipoprotein
secretion. Inflammatory cytokines also induce dramatic changes in lipid
metabolism, particularly in serum triglycerides via increased hepatic
secretion and/or delayed clearance of very low-density lipoprotein. The
aim of this study was to determine whether the mechanism of lipid
dysregulation in the high-fructose diet is induced by stress response
pathways. Animals were fed a high-fructose diet for 14 d to establish
hypertriglyceridemia and then were treated with lipoxygenase inhibitors
for 4 d concurrent with the diet. At the end of drug treatment, the
animals were divided into two groups and treated with lipopolysaccharide
or a vehicle. Serum samples were taken pretreatment and posttreatment,
and liver tissue was harvested at the end of study. Serum samples were
tested for metabolic parameters, and the tissue samples were tested for
metabolic and stress pathway responses. Our results show that
fructose-fed rats have changes in the c-Jun N-terminal kinase pathway
with correspondingly elevated activator protein-1 activity, consistent
with an inflammatory response. Treatment with lipoxygenase inhibitors
reversed the hypertriglyceridemia and also reduced activator protein-1
activation, suggesting that the basis for lipid dysregulation in this
model is due to activation of inflammatory pathways in the liver.
PMID: 14576175 [PubMed - in process]
]