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Hepatic Mediators of Lipid Metabolism and Ketogenesis: Focus on Fatty Liver and Diabetes


Gustavo W. Fernandes* and Barbara M. L. C. Bocco   Pages 1 - 12 ( 12 )


Background: Diabetes mellitus (DM) is a chronic disorder that it is caused by the absence of insulin secretion due to the inability of the pancreas to produce it (type 1 diabetes; T1DM), or due to defects of insulin signaling in the peripheral tissues, resulting in insulin resistance (type 2 diabetes; T2DM). Commonly, the occurrence of insulin resistance in T2DM patients reflects the high prevalence of obesity and non-alcoholic fatty liver disease (NAFLD) manifestation in these individuals. In fact, approximately 60% T2DM patients are also diagnosed to have NAFLD, and this condition is strongly linked with insulin resistance and obesity. NAFLD is the hepatic manifestation of obesity and metabolic syndrome and includes a spectrum of pathological conditions, which range from simple steatosis (NAFL), nonalcoholic steatohepatitis (NASH), and cirrhosis and hepatocellular carcinoma. NAFLD manifestation is followed by a series of hepatic lipid deregulations and the main abnormalities are increased triglyceride levels, increased hepatic production of VLDL and a reduction of VLDL catabolism. During the progression of NAFLD, the production of ketone bodies progressively reduces while hepatic glucose synthesis and output increases. In fact, most of the fat that enters the liver can be disposed through ketogenesis, preventing the development of NAFLD and hyperglycemia.

Objective: This review will focus on the pathophysiological aspect of hepatic lipid metabolism deregulation, ketogenesis and its relevance in progression of NAFLD and T2DM.

Conclusion: A better understanding of the molecular mediators involved in lipid synthesis and ketogenesis can lead to new treatments for metabolic disorders in the liver, such as NAFLD.


Type 2 diabetes, steatosis, NAFLD and ketogenesis


Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Chicago, Chicago IL, Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Chicago, Chicago IL

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