Hepatic ABC transporters and triglyceride metabolism

John S. Parks, Soonkyu Chung, Gregory S. Shelness

Research output: Contribution to journalReview article

15 Citations (Scopus)

Abstract

PURPOSE OF REVIEW: Elevated plasma triglyceride and reduced HDL concentrations are prominent features of metabolic syndrome and type 2 diabetes. Individuals with Tangier disease also have elevated plasma triglyceride concentrations and very low HDL, resulting from mutations in ATP-binding cassette transporter A1 (ABCA1), an integral membrane protein that facilitates nascent HDL particle assembly. Past studies attributed the inverse relationship between plasma HDL and triglyceride to intravascular lipid exchange and catabolic events. However, recent studies also suggest that hepatic signaling and lipid mobilization and secretion may explain how HDL affects plasma triglyceride concentrations. RECENT FINDINGS: Hepatocyte-specific ABCA1 knockout mice have markedly reduced plasma HDL and a two-fold increase in triglyceride due to failure to assemble nascent HDL particles by hepatocytes, causing increased catabolism of HDL apolipoprotein A-I and increased hepatic production of triglyceride-enriched VLDL. In-vitro studies suggest that nascent HDL particles may induce signaling to decrease triglyceride secretion. Inhibition of microRNA 33 expression in nonhuman primates augments hepatic ABCA1, genes involved in fatty acid oxidation, and decreases expression of lipogenic genes, causing increased plasma HDL and decreased triglyceride levels. SUMMARY: New evidence suggests potential mechanisms by which hepatic ABCA1-mediated nascent HDL formation regulates VLDL-triglyceride production and contributes to the inverse relationship between plasma HDL and triglyceride.

Original languageEnglish (US)
Pages (from-to)196-200
Number of pages5
JournalCurrent Opinion in Lipidology
Volume23
Issue number3
DOIs
StatePublished - Jun 1 2012

Fingerprint

ATP-Binding Cassette Transporters
Pre-beta High-Density Lipoprotein
Triglycerides
Liver
Hepatocytes
Tangier Disease
Lipid Mobilization
Apolipoprotein A-I
MicroRNAs
Knockout Mice
Type 2 Diabetes Mellitus
Primates
Membrane Proteins
Fatty Acids
Lipids
Gene Expression
Mutation

Keywords

  • ATP-binding cassette transporter A1
  • Tangier disease
  • high-density lipoprotein formation
  • mRNA
  • very low-density lipoprotein production

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Genetics
  • Nutrition and Dietetics
  • Cardiology and Cardiovascular Medicine
  • Cell Biology

Cite this

Hepatic ABC transporters and triglyceride metabolism. / Parks, John S.; Chung, Soonkyu; Shelness, Gregory S.

In: Current Opinion in Lipidology, Vol. 23, No. 3, 01.06.2012, p. 196-200.

Research output: Contribution to journalReview article

Parks, John S. ; Chung, Soonkyu ; Shelness, Gregory S. / Hepatic ABC transporters and triglyceride metabolism. In: Current Opinion in Lipidology. 2012 ; Vol. 23, No. 3. pp. 196-200.
@article{600990ce713b4effa5f061ccb498320b,
title = "Hepatic ABC transporters and triglyceride metabolism",
abstract = "PURPOSE OF REVIEW: Elevated plasma triglyceride and reduced HDL concentrations are prominent features of metabolic syndrome and type 2 diabetes. Individuals with Tangier disease also have elevated plasma triglyceride concentrations and very low HDL, resulting from mutations in ATP-binding cassette transporter A1 (ABCA1), an integral membrane protein that facilitates nascent HDL particle assembly. Past studies attributed the inverse relationship between plasma HDL and triglyceride to intravascular lipid exchange and catabolic events. However, recent studies also suggest that hepatic signaling and lipid mobilization and secretion may explain how HDL affects plasma triglyceride concentrations. RECENT FINDINGS: Hepatocyte-specific ABCA1 knockout mice have markedly reduced plasma HDL and a two-fold increase in triglyceride due to failure to assemble nascent HDL particles by hepatocytes, causing increased catabolism of HDL apolipoprotein A-I and increased hepatic production of triglyceride-enriched VLDL. In-vitro studies suggest that nascent HDL particles may induce signaling to decrease triglyceride secretion. Inhibition of microRNA 33 expression in nonhuman primates augments hepatic ABCA1, genes involved in fatty acid oxidation, and decreases expression of lipogenic genes, causing increased plasma HDL and decreased triglyceride levels. SUMMARY: New evidence suggests potential mechanisms by which hepatic ABCA1-mediated nascent HDL formation regulates VLDL-triglyceride production and contributes to the inverse relationship between plasma HDL and triglyceride.",
keywords = "ATP-binding cassette transporter A1, Tangier disease, high-density lipoprotein formation, mRNA, very low-density lipoprotein production",
author = "Parks, {John S.} and Soonkyu Chung and Shelness, {Gregory S.}",
year = "2012",
month = "6",
day = "1",
doi = "10.1097/MOL.0b013e328352dd1a",
language = "English (US)",
volume = "23",
pages = "196--200",
journal = "Current Opinion in Lipidology",
issn = "0957-9672",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - Hepatic ABC transporters and triglyceride metabolism

AU - Parks, John S.

AU - Chung, Soonkyu

AU - Shelness, Gregory S.

PY - 2012/6/1

Y1 - 2012/6/1

N2 - PURPOSE OF REVIEW: Elevated plasma triglyceride and reduced HDL concentrations are prominent features of metabolic syndrome and type 2 diabetes. Individuals with Tangier disease also have elevated plasma triglyceride concentrations and very low HDL, resulting from mutations in ATP-binding cassette transporter A1 (ABCA1), an integral membrane protein that facilitates nascent HDL particle assembly. Past studies attributed the inverse relationship between plasma HDL and triglyceride to intravascular lipid exchange and catabolic events. However, recent studies also suggest that hepatic signaling and lipid mobilization and secretion may explain how HDL affects plasma triglyceride concentrations. RECENT FINDINGS: Hepatocyte-specific ABCA1 knockout mice have markedly reduced plasma HDL and a two-fold increase in triglyceride due to failure to assemble nascent HDL particles by hepatocytes, causing increased catabolism of HDL apolipoprotein A-I and increased hepatic production of triglyceride-enriched VLDL. In-vitro studies suggest that nascent HDL particles may induce signaling to decrease triglyceride secretion. Inhibition of microRNA 33 expression in nonhuman primates augments hepatic ABCA1, genes involved in fatty acid oxidation, and decreases expression of lipogenic genes, causing increased plasma HDL and decreased triglyceride levels. SUMMARY: New evidence suggests potential mechanisms by which hepatic ABCA1-mediated nascent HDL formation regulates VLDL-triglyceride production and contributes to the inverse relationship between plasma HDL and triglyceride.

AB - PURPOSE OF REVIEW: Elevated plasma triglyceride and reduced HDL concentrations are prominent features of metabolic syndrome and type 2 diabetes. Individuals with Tangier disease also have elevated plasma triglyceride concentrations and very low HDL, resulting from mutations in ATP-binding cassette transporter A1 (ABCA1), an integral membrane protein that facilitates nascent HDL particle assembly. Past studies attributed the inverse relationship between plasma HDL and triglyceride to intravascular lipid exchange and catabolic events. However, recent studies also suggest that hepatic signaling and lipid mobilization and secretion may explain how HDL affects plasma triglyceride concentrations. RECENT FINDINGS: Hepatocyte-specific ABCA1 knockout mice have markedly reduced plasma HDL and a two-fold increase in triglyceride due to failure to assemble nascent HDL particles by hepatocytes, causing increased catabolism of HDL apolipoprotein A-I and increased hepatic production of triglyceride-enriched VLDL. In-vitro studies suggest that nascent HDL particles may induce signaling to decrease triglyceride secretion. Inhibition of microRNA 33 expression in nonhuman primates augments hepatic ABCA1, genes involved in fatty acid oxidation, and decreases expression of lipogenic genes, causing increased plasma HDL and decreased triglyceride levels. SUMMARY: New evidence suggests potential mechanisms by which hepatic ABCA1-mediated nascent HDL formation regulates VLDL-triglyceride production and contributes to the inverse relationship between plasma HDL and triglyceride.

KW - ATP-binding cassette transporter A1

KW - Tangier disease

KW - high-density lipoprotein formation

KW - mRNA

KW - very low-density lipoprotein production

UR - http://www.scopus.com/inward/record.url?scp=84861094609&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84861094609&partnerID=8YFLogxK

U2 - 10.1097/MOL.0b013e328352dd1a

DO - 10.1097/MOL.0b013e328352dd1a

M3 - Review article

C2 - 22488425

AN - SCOPUS:84861094609

VL - 23

SP - 196

EP - 200

JO - Current Opinion in Lipidology

JF - Current Opinion in Lipidology

SN - 0957-9672

IS - 3

ER -