The liver is an exceptionally complex and diverse organ that functions both as an exocrine and an endocrine gland. It secretes bile, which contains many con stituents in addition to bile salts, and it synthesizes and releases many substances in response to the body's demands, including prohormones, albumin, clotting factors, glucose, fatty acids, and various lipoproteins. It has a dual blood supply providing a rich mixture of nutrients and other absorbed substances via the portal vein and oxygen-rich blood via the hepatic artery. This functional heterogeneity is accompanied by cellular heterogeneity. The liver contains many cell types including hepatic parachymal cells, Kiipffer cells, Ito cells, and endothelial cells. The most abundant cell type, the parenchymal cells, are biochemically and structurally heterogeneous. The cells in the oxygen-rich areas of the portal triad appear more dependent on oxidative metabolism, whereas those around the central vein (pericentral, perivenous, or centrolobular areas) are more dependent upon an anaerobic mechanism. Throughout this volume the latter three terms are used synonymously by various authors to indicate the five to eight layers of cells radiating from the central vein. Structural and metabolic heterogeneity of hepatic parenchymal cells has been demonstrated by a variety of approaches, including histochemical, ultra structural, and ultramicrobiochemical studies. This microheterogeneity is linked to the physiological functions of the liver and its response to injurious substances.

The liver is the largest solid vital organ in mammals that supports other organ in the body in some facet. This book synthesizes all the primary and relevant metabolic information that one needs to review to understand the complex and diverse role of the liver in metabolism. With the current epidemic of metabolic diseases, it is of immediate importance to understand the contribution of the liver in health and its role in the development of impaired metabolic regulation. This book covers the many studies that have unmasked important roles that proteins expressed in the liver play in the development of or protection from metabolic diseases. One of the major metabolic functions of the liver is to carry out de novo lipogenesis, which is the metabolic pathway that allows the conversion of excess carbohydrates into fatty acids. The process of de novo lipogenesis is covered in depth within this volume. The book is an important contribution to the vast literature and ongoing research on liver function.

PGC-1alpha is a transcriptional coactivator selectively expressed in tissues with high metabolic demands and induced by a variety of metabolic stressors, including cold, exercise, and fasting. When expressed, PGC-1alpha can coactivate a number of transcription factors to coordinately activate metabolic pathways that supply tissues and the body with necessary nutrients. PGC-1alpha has emerged as a master controller of mitochondria and many of the processes focused within them, including oxidative phosphorylation, fatty acid oxidation, the TCA cycle and free radical scavenging. PGC-1alpha also induces gluconeogenesis and expression of glucose transporters, thereby regulating blood glucose levels. Given this integral role in modulating energy homeostasis, understanding how PGC-1alpha functions and what factors regulate its activity could help identify processes and proteins that malfunction in various metabolic disorders.