Hepatic fatty acid trafficking: multiple forks in the road - PubMed (original) (raw)

Review

. 2013 Nov 6;4(6):697-710.

doi: 10.3945/an.113.004648. eCollection 2013 Nov.

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Review

Hepatic fatty acid trafficking: multiple forks in the road

Douglas G Mashek. Adv Nutr. 2013.

Abstract

The liver plays a unique, central role in regulating lipid metabolism. In addition to influencing hepatic function and disease, changes in specific pathways of fatty acid (FA) metabolism have wide-ranging effects on the metabolism of other nutrients, extra-hepatic physiology, and the development of metabolic diseases. The high prevalence of nonalcoholic fatty liver disease (NAFLD) has led to increased efforts to characterize the underlying biology of hepatic energy metabolism and FA trafficking that leads to disease development. Recent advances have uncovered novel roles of metabolic pathways and specific enzymes in generating lipids important for cellular processes such as signal transduction and transcriptional activation. These studies have also advanced our understanding of key branch points involving FA partitioning between metabolic pathways and have identified new roles for lipid droplets in these events. This review covers recent advances in our understanding of FA trafficking and its regulation. An emphasis will be placed on branch points in these pathways and how alterations in FA trafficking contribute to NAFLD and related comorbidities.

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Conflict of interest statement

Author disclosures: D. G. Mashek, no conflicts of interest.

Figures

FIGURE 1

FIGURE 1

Pathways and enzymes involved in hepatic FA trafficking. Enzymes in red indicate catabolic pathways, whereas blue enzymes are involved in FA disposal. DGAT1 is bicolor, because it may be involved in the synthesis of cytosolic TG from exogenous FA and in VLDL synthesis. ACC1, acetyl-CoA carboxylase 1; ACSL, long chain acyl-CoA synthetase; AGPAT, sn-1-acyl-glycerol-3-phosphate acyltransferase; ATGL, adipose triglyceride lipase; CES, carboxylesterase; CIDEB, cell death-inducing DFF45-like effector B; CPT1a, carnitine palmitoyl transferase 1; CR, chylomicron remnant; DAG, diacylglycerol; DGAT, sn-1,2-diacylglycerol acyltransferase; ELOVL5, long chain fatty acid elongase 5; FA, fatty acid; FAS, fatty acid synthase; FATP, fatty acid transport protein; GPAT, glycerol-3-phosphate acyltransferase; HMGCS2, HMG-CoA synthetase 2; LFABP, liver fatty acid binding protein; LPA, lysophosphatidic acid; MTP, microsomal triglyceride transfer protein; PA, phosphatidic acid; SCD1, stearoyl-CoA desaturase 1.

FIGURE 2

FIGURE 2

Transcriptional and post-transcriptional regulation of hepatic FA trafficking. Green arrows indicate sources of intracellular FA and red arrows indicate routes of FA disposal. AMPK, AMP-activated protein kinase; CHREBP, carbohydrate response element binding protein; CR, chylomicron remnant; FA, fatty acid; FOXA/O, forkhead box protein; FXR, farnesoid X receptor; HNF-4α, hepatocyte nuclear factor-4α LXR, liver X receptor; mTORC1, mammalian target of rapamycin complex 1; SIRT1, sirtuin 1; SREBP, sterol regulatory element binding protein.

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