title: Zonation of hepatic fatty acid metabolism - The diversity of its regulation and the benefit of modeling.
abstract: A pronounced heterogeneity between hepatocytes in subcellular structure and enzyme activities was discovered more than 50years ago and initiated the idea of metabolic zonation. In the last decades zonation patterns of liver metabolism were extensively investigated for carbohydrate, nitrogen and lipid metabolism. The present review focuses on zonation patterns of the latter. We review recent findings regarding the zonation of fatty acid uptake and oxidation, ketogenesis, triglyceride synthesis and secretion, de novo lipogenesis, as well as bile acid and cholesterol metabolism. In doing so, we expose knowledge gaps and discuss contradictory experimental results, for example on the zonation pattern of fatty acid oxidation and de novo lipogenesis. Thus, possible rewarding directions of further research are identified. Furthermore, recent findings about the regulation of metabolic zonation are summarized, especially regarding the role of hormones, nerve innervation, morphogens, gender differences and the influence of the circadian clock. In the last part of the review, a short collection of models considering hepatic lipid metabolism is provided. We conclude that modeling, despite its proven benefit for understanding of hepatic carbohydrate and ammonia metabolisms, has so far been largely disregarded in the study of lipid metabolism; therefore some possible fields of modeling interest are presented.
authors: Department of Bioinformatics, University of Jena, Jena, Germany. Electronic address: janaschleicher@gmail.com.
authors: J
authors: J
authors: Schleicher
authors: Department of Bioinformatics, University of Jena, Jena, Germany.
authors: C
authors: C
authors: Tokarski
authors: Institute of Biochemistry, Faculty of Medicine, University of Leipzig, Leipzig, Germany.
authors: E
authors: E
authors: Marbach
authors: Institute of Biochemistry, Faculty of Medicine, University of Leipzig, Leipzig, Germany.
authors: M
authors: M
authors: Matz-Soja
authors: Department of Chemicals and Product Safety, German Federal Institute for Risk Assessment (BfR), Berlin, Germany.
authors: S
authors: S
authors: Zellmer
authors: Institute of Biochemistry, Faculty of Medicine, University of Leipzig, Leipzig, Germany.
authors: R
authors: R
authors: Gebhardt
authors: Department of Bioinformatics, University of Jena, Jena, Germany.
authors: S
authors: S
authors: Schuster
mesh_terms: D000818:Animals; D005227:Fatty Acids / Q000378:metabolism*; D022781:Hepatocytes / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D008099:Liver / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D008954:Models, Biological
chemical_list: D005227:Fatty Acids
keywords: Fatty acid metabolism; Liver; Metabolic zonation