oa Hepatic Glucose and Fatty Acid Metabolism

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The liver is a vital organ involved in the preservation of the balance among the metabolic functions of the whole-body. Liver metabolism is complex and most difficult to investigate or to monitor, and only indirect measurements have been available in human beings for a long time. This is due to the peculiar anatomical location of the liver, since circulating substrates reach the organ via the hepatic artery and the portal vein, the latter being not accessible for routine measurements. Recently, PET imaging has been introduced to characterize liver glucose and fatty acid metabolism. Mathematical modelling of liver metabolism by use of PET and [18F]fluoro-2-deoxy-D-glucose (18F-FDG) or [11C]Palmitate (11C-palmitate) has been recently validated, and the requirement of a dual (arterial and portal venous) input function has led to the development of approaches for its estimation. The application of the methodology to the understanding of human metabolic disorders (obesity, impaired glucose tolerance, diabetes) highlights a tight reciprocal regulation between glucose and fatty acid metabolism, suggesting that the liver is first engaged in counterbalancing the overflow of fatty acids deriving from a dysfunctional adipose tissue, by the activation and/or exhaustion of oxidation and lipid accumulation. These events may compromise hepatic insulin action and glucose metabolism. Once chronic hyperglycaemia ensues, the capability of the liver to utilize fatty acids during fasting and glucose during insulin stimulation may become further defective. This chapter describes the methodological advances, and the clinical findings so far achieved by PET imaging in the field of liver metabolism in metabolic diseases.