Lipid-Liver Crosstalk in Health and Disease

The liver is a major metabolic organ, essentially controlling glucose and fat metabolism. Because lipids are water-insoluble, they need to be transported in the circulation in association with proteins in the form of lipoproteins. These lipoproteins play a key role in the absorption and transport of dietary lipids by the small intestine, in the transport of lipids from the liver to peripheral tissues, and in the transport of lipids from peripheral tissues to the liver and intestine. Upon feeding, energy is provided by glycolysis and the unused glucose is stored as glycogen in the liver. Excess glucose is used to synthesize fatty acids through de novo lipogenesis. Fatty acids are incorporated into triacylglycerol, phospholipids, or cholesterol esters in hepatocytes. These complex lipids are stored in lipid droplets or secreted into the circulation as very low-density lipoprotein particles. Upon fasting, after consumption of stored glycogen, the liver secretes glucose through gluconeogenesis. Fasting also promotes lipolysis in adipose tissue, resulting in release of free fatty acids which are metabolized in hepatic mitochondria though beta-oxidation for energy production, while excess fatty acids are stored by the liver leading to hepatic steatosis. Disturbances in lipid metabolism, as in alcoholic and non-alcoholic steatohepatitis, obesity and diabetes, will affect liver performance and function. Likewise, disturbed liver functions by acute or chronic liver disease, as in viral hepatitis, will affect lipid homeostasis. This may carry an increased risk of atherosclerosis and ischemic heart disease which may endanger life. Dietary restriction or fasting was found to have a positive impact on restoring lipid homeostasis leading to improved quality of life.