Article detail · 2012
Uric Acid Induces Hepatic Steatosis by Generation of Mitochondrial Oxidative Stress POTENTIAL ROLE IN FRUCTOSE DEPENDENT AND INDEPENDENT FATTY LIVER
- Year
- 2012
- Type
- article
Data source split
- YÖKSİS YÖKSİS article record
- YÖKSİS venue Journal of Biological Chemistry
- Catalog match (ISSN) Journal of Biological Chemistry
- OpenAlex OpenAlex enrichment (abstract, citations, topics)
Abstract
OpenAlex · English
BACKGROUND: Uric acid is an independent risk factor in fructose-induced fatty liver, but whether it is a marker or a cause remains unknown. RESULTS: Hepatocytes exposed to uric acid developed mitochondrial dysfunction and increased de novo lipogenesis, and its blockade prevented fructose-induced lipogenesis. CONCLUSION: Rather than a consequence, uric acid induces fatty liver SIGNIFICANCE: Hyperuricemic people are more prone to develop fructose-induced fatty liver. Metabolic syndrome represents a collection of abnormalities that includes fatty liver, and it currently affects one-third of the United States population and has become a major health concern worldwide. Fructose intake, primarily from added sugars in soft drinks, can induce fatty liver in animals and is epidemiologically associated with nonalcoholic fatty liver disease in humans. Fructose is considered lipogenic due to its ability to generate triglycerides as a direct consequence of the metabolism of the fructose molecule. Here, we show that fructose also stimulates triglyceride synthesis via a purine-degrading pathway that is triggered from the rapid phosphorylation of fructose by fructokinase. Generated AMP enters into the purine degradation pathway through the activation of AMP deaminase resulting in uric acid production and the generation of mitochondrial oxidants. Mitochondrial oxidative stress results in the inhibition of aconitase in the Krebs cycle, resulting in the accumulation of citrate and the stimulation of ATP citrate lyase and fatty-acid synthase leading to de novo lipogeneis. These studies provide new insights into the pathogenesis of hepatic fat accumulation under normal and diseased states.
Topics
Citations
OpenAlex cited_by_count. Not a WoS or Scopus citation count; those sources have no separate column here.
715 citations
OpenAlex cited_by_count (cache / database)
28 publications in the local catalog that cite this work (OpenAlex reference match; not the full global list).
- Lowering Uric Acid with Allopurinol Improves Insulin Resistance and Systemic Inflammation in Asymptomatic Hyperuricemia 2015
- Lowering Uric Acid With Allopurinol Improves Insulin Resistance and Systemic Inflammation in Asymptomatic Hyperuricemia 2015
- Lowering Uric Acid With Allopurinol Improves Insulin Resistance and Systemic Inflammation in Asymptomatic Hyperuricemia 2015
- Lowering Uric Acid with Allopurinol Improves Insulin Resistance and Systemic Inflammation in Asymptomatic Hyperuricemia 2015
- Lowering Uric Acid With Allopurinol Improves Insulin Resistance and Systemic Inflammation in Asymptomatic Hyperuricemia 2015
- The association between serum uric acid to high density lipoprotein-cholesterol ratio and non-alcoholic fatty liver disease: the abund study 2021
- The association between serum uric acid to high density lipoprotein-cholesterol ratio and non-alcoholic fatty liver disease: the abund study 2021
- The association between serum uric acid to high density lipoprotein-cholesterol ratio and non-alcoholic fatty liver disease: the abund study 2021
- Does mean platelet volume/lymphocyte count ratio associate with frailty in type 2 diabetes mellitus? 2021
- The association between serum uric acid to high density lipoprotein-cholesterol ratio and non-alcoholic fatty liver disease: the abund study 2021