Role of the liver in the control of glucose-lipid utilization and body weight.

Abstract

This review depicts recent developments concerning the role of the liver in control of carbohydrate and lipid utilization from ingestion to storage; it covers the liver's influence on food intake, post-absorptive nutrient metabolism and body weight. The mechanisms involved have implications for the pathogenesis of obesity and type II diabetes. Recent studies have identified some of the molecular and biochemical mechanisms which control whole body and hepatic carbohydrate and lipid metabolism, thus providing the basis of the liver's role in the control of food intake, metabolism, and body weight. Fatty acids are known to effect gene transcription in various ways. Advances in our understanding of the control of glucose and lipid utilization by the liver include (1). a better functional characterization of some newly discovered transcription factors, (2). new discoveries concerning the physiological and pathophysiological role of hepatic glucokinase and of the glycogen-targeting subunits of protein phosphatase-1, and (3). the demonstration of substantial overlap in the molecular control mechanisms of glucose-lipid utilization. Also, impaired insulin signaling due to a certain gene (Foxo1) has emerged as a possible unifying mechanism for various common metabolic abnormalities of type II diabetes. Finally, recent findings confirm and extend previous knowledge about the important role of hepatic nerves in the control of liver and whole body glucose-lipid utilization. The identification of new molecular and neural mechanisms of the hepatic control of glucose-lipid utilization and body weight provides a focus for future studies and may eventually help to develop new treatments for obesity and type II diabetes.