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Semin Liver Dis 2015; 35(03): 250-261
DOI: 10.1055/s-0035-1562945
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Fatty Acid and Glucose Sensors in Hepatic Lipid Metabolism: Implications in NAFLD

Michele Vacca
1   Medical Research Council - Human Nutrition Research (MRC-HNR), Cambridge, United Kingdom
2   Department of Clinical Biochemistry and University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Cambridge, United Kingdom
,
Michael Allison
3   Liver Unit, Department of Medicine, Cambridge Biomedical Research Centre, Cambridge University NHS Foundation Trust, United Kingdom
,
Julian L. Griffin
1   Medical Research Council - Human Nutrition Research (MRC-HNR), Cambridge, United Kingdom
4   Department of Biochemistry, University of Cambridge, United Kingdom
,
Antonio Vidal-Puig
2   Department of Clinical Biochemistry and University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Cambridge, United Kingdom
› Author Affiliations
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Publication History

Publication Date:
17 September 2015 (online)

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Abstract

The term nonalcoholic fatty liver disease (NAFLD) covers a pathologic spectrum from lipid accumulation alone (simple steatosis) to steatosis with associated inflammation and fibrosis (nonalcoholic steatohepatitis [NASH]). Nonalcoholic steatohepatitis can progress to cirrhosis and potentially to hepatocellular carcinoma. Although a genetic predisposition has been highlighted, NAFLD is strongly associated with an unhealthy lifestyle and hypercaloric diet in the context of obesity and metabolic disease. The dysregulation of specific pathways (insulin signaling, mitochondrial function, fatty acid, and lipoprotein metabolism) have been linked to steatosis, but elucidating the molecular events determining evolution of the disease still requires further research before it can be translated into specific personalized interventional strategies. In this review, the authors focus on the early events of the pathophysiology of NASH, dissecting the metabolic and nutritional pathways involving fatty acids and glucose sensors that can modulate lipid accumulation in the liver, but also condition the progression to cirrhosis and hepatocellular carcinoma.

Keywords

insulin resistance - mitochondrial dysfunction - peroxisome proliferator-activated receptors - sterol regulatory element binding protein 1 - carbohydrate response element-binding protein
 

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