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Abstract Details
The importance of keeping time in the liver
Endocrinology. 2020 Dec 15;bqaa230. doi: 10.1210/endocr/bqaa230. Online ahead of print.
Kyle S McCommis1, Andrew A Butler2
Author information
1Department of Biochemistry & Molecular Biology, Center for Cardiovascular Research, Saint Louis University School of Medicine, St. Louis, MO, USA.
2Department of Pharmacology and Physiology, Center for Cardiovascular Research, The Henry and Amelia Nasrallah Center for Neuroscience, School of Medicine and the Henry and Amelia Nasrallah Center for Neuroscience, Saint Louis University, Saint Louis, MO.
Abstract
The liver is a 'front line' in the homeostatic defenses against variation in nutrient intake. It orchestrates metabolic responses to feeding by secreting factors essential for maintaining metabolic homeostasis, converting carbohydrates to triglycerides for storage and releasing lipids packaged as lipoproteins for distribution to other tissues. Between meals, it provides fuel to the body by releasing glucose produced from glucogenic precursors and ketones from fatty acids and ketogenic amino acids. Modern diets enriched in sugars and saturated fats increase lipid accumulation in hepatocytes (nonalcoholic fatty liver disease). If untreated, this can progress to liver inflammation (nonalcoholic steatohepatitis), fibrosis, cirrhosis, and hepatocellular carcinoma. Dysregulation of liver metabolism is also relatively common in modern societies. Increased hepatic glucose production underlies fasting hyperglycemia that defines type 2 diabetes, while increased production of atherogenic large triglyceride-rich very low-density lipoproteins raises the risk of cardiovascular disease. Evidence has accrued of a strong connection between meal timing, the liver clock and metabolic homeostasis. Metabolic programming of the liver transcriptome and post-translation modifications of proteins is strongly influenced by the daily rhythms in nutrient intake governed by the circadian clock. Importantly, while cell-autonomous clocks have been identified in the 2liver, the complete circadian programing of the liver transcriptome and post-translational modifications of essential metabolic proteins is strongly dependent on nutrient flux and circadian signals from outside the liver. The purpose of this review is to provide a basic understanding of liver circadian physiology, drawing attention to recent research on the relationships between circadian biology and liver function.