Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8302050 | Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | 2015 | 16 Pages |
Abstract
A pronounced heterogeneity between hepatocytes in subcellular structure and enzyme activities was discovered more than 50Â years 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.
Keywords
CCGDGAT1diacylglycerol acyltransferase 1FATP3-hydroxy-3-methylglutaryl CoASCD1DNLL-FABPVLDLHNF1αSREBF1brain and muscle ARNT-like 1ELOVLHMG-CoAATP-citrate lyaseSCNFFAACCRORAMPKFASAPCFatty acid translocase/cluster of differentiation 36hepatocyte nuclear factor 1αPPARSterol regulatory element-binding transcription factor 1NAFLDBmal1FAT/CD36adenomatous polyposis coliStearoyl-CoA desaturase 1acetyl-CoA carboxylaseFatty acidFree fatty acidfatty acid synthasenon-alcoholic fatty liver diseasestriglycerideMetabolic zonationACLClockForkhead transcription factorsFoxOvery-low-density lipoproteinsFatty acid metabolismNADnicotinamide adenine dinucleotideSuprachiasmatic nucleiFatty acid transport proteinTCA cyclecircadian locomotor output cycles kaputLiverperoxisome proliferator-activated receptorNuclear receptor
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Authors
J. Schleicher, C. Tokarski, E. Marbach, M. Matz-Soja, S. Zellmer, R. Gebhardt, S. Schuster,