Gene/Protein Disease Symptom Drug Enzyme Compound
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Rates of fructose consumption continue to rise nationwide and have been linked to rising rates of obesity, type 2 diabetes, and metabolic syndrome. Because obesity has been equated with addiction, and because of their evolutionary commonalities, we chose to examine the metabolic, hedonic, and societal similarities between fructose and its fermentation byproduct ethanol. Elucidation of fructose metabolism in liver and fructose action in brain demonstrate three parallelisms with ethanol. First, hepatic fructose metabolism is similar to ethanol, as they both serve as substrates for de novo lipogenesis, and in the process both promote hepatic insulin resistance, dyslipidemia, and hepatic steatosis. Second, fructosylation of proteins with resultant superoxide formation can result in hepatic inflammation similar to acetaldehyde, an intermediary metabolite of ethanol. Lastly, by stimulating the "hedonic pathway" of the brain both directly and indirectly, fructose creates habituation, and possibly dependence; also paralleling ethanol. Thus, fructose induces alterations in both hepatic metabolism and central nervous system energy signaling, leading to a "vicious cycle" of excessive consumption and disease consistent with metabolic syndrome. On a societal level, the treatment of fructose as a commodity exhibits market similarities to ethanol. Analogous to ethanol, societal efforts to reduce fructose consumption will likely be necessary to combat the obesity epidemic.
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PMID:Fructose: metabolic, hedonic, and societal parallels with ethanol. 2170 74

The Systems Genetics Resource (SGR) (http://systems.genetics.ucla.edu) is a new open-access web application and database that contains genotypes and clinical and intermediate phenotypes from both human and mouse studies. The mouse data include studies using crosses between specific inbred strains and studies using the Hybrid Mouse Diversity Panel. SGR is designed to assist researchers studying genes and pathways contributing to complex disease traits, including obesity, diabetes, atherosclerosis, heart failure, osteoporosis, and lipoprotein metabolism. Over the next few years, we hope to add data relevant to deafness, addiction, hepatic steatosis, toxin responses, and vascular injury. The intermediate phenotypes include expression array data for a variety of tissues and cultured cells, metabolite levels, and protein levels. Pre-computed tables of genetic loci controlling intermediate and clinical phenotypes, as well as phenotype correlations, are accessed via a user-friendly web interface. The web site includes detailed protocols for all of the studies. Data from published studies are freely available; unpublished studies have restricted access during their embargo period.
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PMID:The systems genetics resource: a web application to mine global data for complex disease traits. 2373 Mar 5

Nonalcoholic fatty liver disease (NAFLD) is an emerging entity, becoming the most prevalent pediatric chronic liver disease. Its broad spectrum of histological findings, comorbidities, and complications, including cirrhosis and liver failure, can occur in childhood, emphasizing the severity of pediatric NAFLD. Current lifestyle and diet modifications have been linked to the increasing prevalence of NAFLD, including the rise of fructose consumption, a monosaccharide present in foods that contain added sugar, such as sugar-sweetened beverages. Excessive fructose consumption is believed to cause addiction like alcohol and other drugs. As such, the new term "fructoholism" refers to the consumption of a substance (fructose) that can cause psychological and physical damage and become a major public health concern, highlighting the seriousness of the excessive consumption of fructose in the pediatric age. Hepatic fructose metabolization leads to hepatic steatosis and progression to fibrosis through mechanisms comparable to alcoholic liver disease, hence the term "fructoholic liver disease." Conclusion: The importance of implementing reliable global strategies, such as education campaigns to promote healthy diet, increasing taxes on foods that contain added sugars, subsidies to promote accessibility to fruit and vegetables, and strict food industry regulation to reduce sugar intake in children and adolescents, cannot be overemphasized.
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PMID:Childhood Fructoholism and Fructoholic Liver Disease. 3061 93

Introduction The purpose of this study was to discern the pattern of alcohol consumption and the severity of alcohol-related liver disease (ARLD) in patients visiting the tertiary care hospital. Methods A cross-sectional study was conducted at Dr. Ziauddin Hospital Clifton campus, Karachi. Patients visiting the liver clinic with disturbed liver enzymes and a history of alcohol intake after excluding other causes were included. A detailed history, routine investigations, insulin level, abdominal ultrasound, and transient elastography were performed. Results A total of 155 patients were included in the study, 98% of whom were men. The median age was 45.93 years (range: 18-78 years). Just over three-fourths of the visiting patients were Muslim (n=119; 76.8%). The median duration of alcohol intake was 5.7 years. All patients admitted to consuming alcohol on an empty stomach before dinner. The most common associated addiction was smoking (n=95; 61.2%). Around two-thirds of patients confessed to binge drinking (n=66; 42.9%). According to the Diagnostic and Statistical Manual of Mental Disorders criteria, 92 patients (59.35%) were alcohol dependent. Hepatic steatosis was positively correlated with the weight of patients (p=0.035). Other factors positively correlated with hepatic steatosis included insulin resistance (p=0.031), elevated uric acid levels (p=0.003), and units of alcohol intake (p=0.054). Significant fibrosis (F3-F4) was present in 73 (47.09%) patients. It was correlated with low platelet count, total bilirubin, aspartate aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, international normalized ratio, albumin, uric acid, controlled attenuation parameter, and units of alcohol intake with significant p-values. Further multivariant analysis showed liver fibrosis was correlated with cholesterol level with a significant p-value (p=0.045). Conclusion ARLD is mainly a male-dominant disease in our population. Most patients consumed a large volume of highly concentrated alcohol and were alcohol dependent. Insulin resistance was observed in a significant number of patients.
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PMID:The Pattern of Alcohol Consumption and the Severity of Alcohol-related Liver Disease in Patients Visiting the Liver Clinic. 3229 65