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      The association between serum uric acid to high density lipoprotein-cholesterol ratio and non-alcoholic fatty liver disease: the abund study

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          Abstract

          SUMMARY OBJECTIVE: Non-alcoholic fatty liver disease, which is characterized by lipid being deposited into hepatocytes, affects nearly one in three adults globally. Inflammatory markers were suggested to be related with hepatic steatosis. Uric acid to HDL cholesterol ratio is proposed as a novel inflammatory and metabolic marker. We aimed to compare Uric acid to HDL cholesterol ratio levels of patients with Non-alcoholic fatty liver disease to those of healthy controls and find out potential correlations between Uric acid to HDL cholesterol ratio and other inflammatory and metabolic markers of Non-alcoholic fatty liver disease. METHODS: Patients with a diagnosis of Non-alcoholic fatty liver disease who were on clinical follow-up in our institution were enrolled in the study as the Non-alcoholic fatty liver disease group, while healthy volunteers were enrolled as the control group. The Uric acid to HDL cholesterol ratio of the groups was compared and potential correlations were studied between Uric acid to HDL cholesterol ratio and fasting blood glucose, transaminases, serum lipids (triglyceride, LDL-cholesterol), weight, and body mass index. RESULTS: The Uric acid to HDL cholesterol ratio of the Non-alcoholic fatty liver disease (13±5%) group was significantly higher compared to the Uric acid to HDL cholesterol ratio of the control (10±4%) group (p<0.001). Uric acid to HDL cholesterol ratio was significantly and positively correlated with fasting blood glucose, transaminases, triglyceride, body weight, waist circumference, hip circumference, and body mass index. A ROC analysis revealed that a Uric acid to HDL cholesterol ratio level greater than 9.6% has 73% sensitivity and 51% specificity in determining Non-alcoholic fatty liver disease. CONCLUSION: Due to the inexpensive and easy-to-assess nature of Uric acid to HDL cholesterol ratio, we suggest that elevated Uric acid to HDL cholesterol ratio levels be considered a useful tool in diagnosing hepatic steatosis.

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          Most cited references30

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          Molecular mechanism of PPARα action and its impact on lipid metabolism, inflammation and fibrosis in non-alcoholic fatty liver disease.

          Peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor belonging, together with PPARγ and PPARβ/δ, to the NR1C nuclear receptor subfamily. Many PPARα target genes are involved in fatty acid metabolism in tissues with high oxidative rates such as muscle, heart and liver. PPARα activation, in combination with PPARβ/δ agonism, improves steatosis, inflammation and fibrosis in pre-clinical models of non-alcoholic fatty liver disease, identifying a new potential therapeutic area. In this review, we discuss the transcriptional activation and repression mechanisms by PPARα, the spectrum of target genes and chromatin-binding maps from recent genome-wide studies, paying particular attention to PPARα-regulation of hepatic fatty acid and plasma lipoprotein metabolism during nutritional transition, and of the inflammatory response. The role of PPARα, together with other PPARs, in non-alcoholic steatohepatitis will be discussed in light of available pre-clinical and clinical data.
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            Uric acid induces hepatic steatosis by generation of mitochondrial oxidative stress: potential role in fructose-dependent and -independent fatty liver.

            Uric acid is an independent risk factor in fructose-induced fatty liver, but whether it is a marker or a cause remains unknown. Hepatocytes exposed to uric acid developed mitochondrial dysfunction and increased de novo lipogenesis, and its blockade prevented fructose-induced lipogenesis. Rather than a consequence, uric acid induces fatty liver 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.
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              Molecular identification of a danger signal that alerts the immune system to dying cells.

              In infections, microbial components provide signals that alert the immune system to danger and promote the generation of immunity. In the absence of such signals, there is often no immune response or tolerance may develop. This has led to the concept that the immune system responds only to antigens perceived to be associated with a dangerous situation such as infection. Danger signals are thought to act by stimulating dendritic cells to mature so that they can present foreign antigens and stimulate T lymphocytes. Dying mammalian cells have also been found to release danger signals of unknown identity. Here we show that uric acid is a principal endogenous danger signal released from injured cells. Uric acid stimulates dendritic cell maturation and, when co-injected with antigen in vivo, significantly enhances the generation of responses from CD8+ T cells. Eliminating uric acid in vivo inhibits the immune response to antigens associated with injured cells, but not to antigens presented by activated dendritic cells. Our findings provide a molecular link between cell injury and immunity and have important implications for vaccines, autoimmunity and inflammation.
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                Author and article information

                Journal
                ramb
                Revista da Associação Médica Brasileira
                Rev. Assoc. Med. Bras.
                Associação Médica Brasileira (São Paulo, SP, Brazil )
                0104-4230
                1806-9282
                April 2021
                : 67
                : 4
                : 549-554
                Affiliations
                [2] Bolu orgnameAbant Izzet Baysal University Hospital orgdiv1Department of Internal Medicine Turkey
                [1] Bolu orgnameAbant Izzet Baysal University Hospital orgdiv1Department of Internal Medicine and Gastroenterology Turkey
                Article
                S0104-42302021000500549 S0104-4230(21)06700400549
                10.1590/1806-9282.20201005
                34495059
                ecd2a15d-c7c2-4c31-84a6-9fc10d16bbdd

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 15 December 2020
                : 24 December 2020
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 30, Pages: 6
                Product

                SciELO Brazil

                Categories
                Original Article

                HDL cholesterol,Inflammation,Liver steatosis,Uric acid
                HDL cholesterol, Inflammation, Liver steatosis, Uric acid

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