Lipidomic Dissection of Nonalcoholic Steatohepatitis: Moving Beyond Foie Gras to Fat Traffic

Bass, Nathan M.

doi:10.1002/hep.23458

Cited by 22 publications

(22 citation statements)

References 21 publications

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“…Inappropriate triglyceride synthesis may, therefore, contribute to the development of NASH, which can progress to liver cirrhosis, hepatic failure and hepatocellular carcinoma. This assumption is in line with the observation that triglycerides drop during progression of NASH to liver cirrhosis [1]. NAFLD is commonly associated with hepatic insulin resistance and a functional role of ceramides and diacylglycerols is being discussed herein [3,4].…”

Section: Nonalcoholic Fatty Liver Diseasesupporting

confidence: 55%

“…Regarding the higher toxicity of SFA this may represent an adaptive response to increased FA in NAFLD [1]. This compensatory mechanism seems not to be effective in morbidly obese patients where SFA species are raised [8].…”

Section: Circulating Lipids In Nafldmentioning

confidence: 99%

“…Fatty liver is a relatively benign condition and is characterized by the accumulation of lipids in liver parenchymal cells. Triglycerides are strongly elevated and their synthesis is suggested to protect from the harmful effects of free fatty acids and its derivatives [1,2]. Inappropriate triglyceride synthesis may, therefore, contribute to the development of NASH, which can progress to liver cirrhosis, hepatic failure and hepatocellular carcinoma.…”

Section: Nonalcoholic Fatty Liver Diseasementioning

confidence: 99%

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Regard Lipidomics in human nonalcoholic fatty liver disease

Buechler¹

2014

Clinical Lipidology

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Section: Nonalcoholic Fatty Liver Diseasesupporting

confidence: 55%

Section: Circulating Lipids In Nafldmentioning

confidence: 99%

Section: Nonalcoholic Fatty Liver Diseasementioning

confidence: 99%

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Regard Lipidomics in human nonalcoholic fatty liver disease

Buechler¹

2014

Clinical Lipidology

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“…Lipidomic analyses of human fatty livers have identified free cholesterol (FC) but not free fatty acids (FFA), diacylglycerides (DAG) or ceramide among the potential lipotoxic molecules that accumulate selectively in NASH but not in "not NASH' NAFLD livers 84,91,93-95. Lysophosphatidylcholine has also been implicated in a small study 95.…”

Section: Hepatocyte Stressesmentioning

confidence: 99%

NASH is an Infl ammatory Disorder: Pathogenic, Prognostic and Therapeutic Implications

Farrell

Rooyen²,

Gan³

et al. 2012

Gut Liver

345

274

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While non-alcoholic fatty liver disease (NAFLD) is highly prevalent (15% to 45%) in modern societies, only 10% to 25% of cases develop hepatic fibrosis leading to cirrhosis, end-stage liver disease or hepatocellular carcinoma. Apart from pre-existing fibrosis, the strongest predictor of fibrotic progression in NAFLD is steatohepatitis or non-alcoholic steatohepatitis (NASH). The critical features other than steatosis are hepatocellular degeneration (ballooning, Mallory hyaline) and mixed inflammatory cell infiltration. While much is understood about the relationship of steatosis to metabolic factors (over-nutrition, insulin resistance, hyperglycemia, metabolic syndrome, hypoadiponectinemia), less is known about inflammatory recruitment, despite its importance for the perpetuation of liver injury and fibrogenesis. In this review, we present evidence that liver inflammation has prognostic significance in NAFLD. We then consider the origins and components of liver inflammation in NASH. Hepatocytes injured by toxic lipid molecules (lipotoxicity) play a central role in the recruitment of innate immunity involving Toll-like receptors (TLRs), Kupffer cells (KCs), lymphocytes and neutrophils and possibly inflammasome. The key pro-inflammatory signaling pathways in NASH are nuclear factor-kappa B (NF-κB) and c-Jun N-terminal kinase (JNK). The downstream effectors include adhesion molecules, chemokines, cytokines and the activation of cell death pathways leading to apoptosis. The upstream activators of NF-κB and JNK are more contentious and may depend on the experimental model used. TLRs are strong contenders. It remains possible that inflammation in NASH originates outside the liver and in the gut microbiota that prime KC/TLR responses, inflamed adipose tissue and circulating inflammatory cells. We briefly review these mechanistic considerations and project their implications for the effective treatment of NASH.

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“…Hepatic and plasma lipidomic ana lysis will probably provide essential and synthetic information on both genetics and lifestyle. On these grounds, it is a very exciting line of research that is likely to promote our understanding of the steps further to lipid accumulation, namely inflammation and fibrogenesis [42], although to date the field remains nascent.…”

Section: Genetics and Lipidomicsmentioning

confidence: 99%