scholarly journals Insulin resistance drives hepatic de novo lipogenesis in nonalcoholic fatty liver disease

2020 ◽  
Vol 130 (3) ◽  
pp. 1453-1460 ◽  
Author(s):  
Gordon I. Smith ◽  
Mahalakshmi Shankaran ◽  
Mihoko Yoshino ◽  
George G. Schweitzer ◽  
Maria Chondronikola ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Nonalcoholic Fatty Liver

scholarly journals Concepts and Treatment Approaches in Nonalcoholic Fatty Liver Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Dina L. Halegoua-De Marzio ◽  
Jonathan M. Fenkel
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
De Novo ◽  
Imaging Techniques ◽  
De Novo Lipogenesis ◽  
Central Adiposity ◽  
Preventative Care ◽  
Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD) affects up to 30% of adults and is the most common liver disease in Western nations. NAFLD is associated with central adiposity, insulin resistance, type 2 diabetes mellitus, hyperlipidemia, and cardiovascular disease. It encompasses the entire spectrum of fatty liver diseases from simple steatosis to nonalcoholic steatohepatitis (NASH) with lobular/portal inflammation, hepatocellular necrosis, and fibrosis. Of those who develop NASH, 15–25% will progress to end stage liver disease and hepatocellular carcinoma over 10–20 years. Its pathogenesis is complex, and involves a state of lipid accumulation due to increased uptake of free fatty acids into the liver, impaired fatty acid beta oxidation, and increased incidence of de novo lipogenesis. Plasma aminotransferases and liver ultrasound are helpful in the diagnosis of NAFLD/NASH, but a liver biopsy is often required for definitive diagnosis. Many new plasma biomarkers and imaging techniques are now available that should improve the ability to diagnose NAFLD noninvasively Due to its complexity and extrahepatic complications, treatment of NAFLD requires a multidisciplinary approach with excellent preventative care, management, and treatment. This review will evaluate our current understanding of NAFLD, with a focus on existing therapeutic approaches and potential pharmacological developments.

scholarly journals Increased De Novo Lipogenesis Is a Distinct Characteristic of Individuals With Nonalcoholic Fatty Liver Disease

2014 ◽  
Vol 146 (3) ◽  
pp. 726-735 ◽  
Author(s):  
Jennifer E. Lambert ◽  
Maria A. Ramos–Roman ◽  
Jeffrey D. Browning ◽  
Elizabeth J. Parks
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Nonalcoholic Fatty Liver

scholarly journals Association between Nicotinamide Phosphoribosyltransferase and de novo Lipogenesis in Nonalcoholic Fatty Liver Disease

2017 ◽  
Vol 26 (3) ◽  
pp. 251-257 ◽  
Author(s):  
Bahareh Amirkalali ◽  
Masoud Reza Sohrabi ◽  
Ali Esrafily ◽  
Mahmoud Jalali ◽  
Ali Gholami ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Nonalcoholic Fatty Liver

scholarly journals Contribution of de novo lipogenesis to the progression of nonalcoholic fatty liver disease

2020 ◽  
Author(s):  
◽  
Majid Mufaqam Syed Abdul
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Liver Enzymes ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Liver Fat ◽  
Percent Reduction ◽  
Nonalcoholic Fatty Liver

This dissertation is focused on understanding the biochemical pathway of de novo lipogenesis (DNL) in humans and how changes in DNL can alter disease states, particularly nonalcoholic fatty liver disease (NAFLD). This document's first chapter presents a review of the literature, while the second chapter focuses on investigating the contribution of DNL to the progression of NAFLD. The main outcome of this study was that as disease severity progressed, hepatic DNL increased in a stepwise fashion until fibrosis was significant, at which time DNL was found to be reduced. Conclusions from isotopic labeling of liver were mirrored by data from protein and gene expression studies which pointed toward mechanisms of promoting both fat storage and decreased fatty acid oxidation. In the third chapter, data are presented on the effects of pharmacological inhibition of DNL, which lowered both liver fat (from 11.8 [percent] to 10.3 [percent]) and liver enzymes (from 29 to 22 U/L). In this study, different subjects received different doses (50, 100, and 15 mg/d) and within the high dose group, DNL was reduced maximally by 75 [percent] which resulted in a 5 [percent] reduction in liver fat and a 36 [percent] reduction in liver enzymes. Lastly, this dissertation's fourth chapter presents data from an investigation in which acute overconsumption of food and alcohol increased liver fat only in individuals whose DNL was stimulated by this treatment but not in individuals with unchanged DNL. The variability in response between subjects was surprising and suggested that for some people, overconsumption of carbohydrates may have greater lipogenic effects than excess alcohol. Future studies should identify the factors that govern this response. In summary, the combined data from these studies highlight the significance of the DNL pathway in promoting increased fat storage in the liver. This conclusion is supported by independent observations of both the negative effects of increased DNL on the liver and the benefits of reducing flux through this pathway to improve liver health. Both dietary and pharmacologic approaches to reduce DNL should be the focus of future treatment of NAFLD.

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