PPAR alpha-activation results in enhanced carnitine biosynthesis and OCTN2-mediated hepatic carnitine accumulation

Naomi van Vlies; Sacha Ferdinandusse; Marjolein Turkenburg; Ronald J. A. Wanders; Frédéric M. Vaz

doi:https://doi.org/10.1016/j.bbabio.2007.07.001

PPAR alpha-activation results in enhanced carnitine biosynthesis and OCTN2-mediated hepatic carnitine accumulation

Naomi van Vlies, Sacha Ferdinandusse, Marjolein Turkenburg, Ronald J. A. Wanders, Frédéric M. Vaz

Amsterdam Gastroenterology Endocrinology Metabolism (AMC)

Research output: Contribution to journal › Article › Academic › peer-review

87 Citations (Scopus)

Abstract

In fasted rodents hepatic carnitine concentration increases considerably which is not observed in PPAR alpha-/- mice, indicating that PPAR alpha is involved in carnitine homeostasis. To investigate the mechanisms underlying the PPAR alpha-dependent hepatic carnitine accumulation we measured carnitine biosynthesis enzyme activities, levels of carnitine biosynthesis intermediates, acyl-carnitines and OCTN2 mRNA levels in tissues of untreated, fasted or Wy-14643-treated wild type and PPAR alpha-/- mice. Here we show that both enhancement of carnitine biosynthesis (due to increased gamma-butyrobetaine dioxygenase activity), extra-hepatic gamma-butyrobetaine synthesis and increased hepatic carnitine import (OCTN2 expression) contributes to the increased hepatic carnitine levels after fasting and that these processes are PPAR alpha-dependent

Original language	English
Pages (from-to)	1134-1142
Journal	BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
Volume	1767
Issue number	9
DOIs	https://doi.org/10.1016/j.bbabio.2007.07.001
Publication status	Published - 2007

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https://doi.org/10.1016/j.bbabio.2007.07.001

Cite this

@article{5f5e99f46eea4db7895f56b56cb8d54a,

title = "PPAR alpha-activation results in enhanced carnitine biosynthesis and OCTN2-mediated hepatic carnitine accumulation",

abstract = "In fasted rodents hepatic carnitine concentration increases considerably which is not observed in PPAR alpha-/- mice, indicating that PPAR alpha is involved in carnitine homeostasis. To investigate the mechanisms underlying the PPAR alpha-dependent hepatic carnitine accumulation we measured carnitine biosynthesis enzyme activities, levels of carnitine biosynthesis intermediates, acyl-carnitines and OCTN2 mRNA levels in tissues of untreated, fasted or Wy-14643-treated wild type and PPAR alpha-/- mice. Here we show that both enhancement of carnitine biosynthesis (due to increased gamma-butyrobetaine dioxygenase activity), extra-hepatic gamma-butyrobetaine synthesis and increased hepatic carnitine import (OCTN2 expression) contributes to the increased hepatic carnitine levels after fasting and that these processes are PPAR alpha-dependent",

author = "{van Vlies}, Naomi and Sacha Ferdinandusse and Marjolein Turkenburg and Wanders, {Ronald J. A.} and Vaz, {Fr{\'e}d{\'e}ric M.}",

year = "2007",

doi = "https://doi.org/10.1016/j.bbabio.2007.07.001",

language = "English",

volume = "1767",

pages = "1134--1142",

journal = "BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS",

issn = "0005-2728",

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number = "9",

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TY - JOUR

T1 - PPAR alpha-activation results in enhanced carnitine biosynthesis and OCTN2-mediated hepatic carnitine accumulation

AU - van Vlies, Naomi

AU - Ferdinandusse, Sacha

AU - Turkenburg, Marjolein

AU - Wanders, Ronald J. A.

AU - Vaz, Frédéric M.

PY - 2007

Y1 - 2007

N2 - In fasted rodents hepatic carnitine concentration increases considerably which is not observed in PPAR alpha-/- mice, indicating that PPAR alpha is involved in carnitine homeostasis. To investigate the mechanisms underlying the PPAR alpha-dependent hepatic carnitine accumulation we measured carnitine biosynthesis enzyme activities, levels of carnitine biosynthesis intermediates, acyl-carnitines and OCTN2 mRNA levels in tissues of untreated, fasted or Wy-14643-treated wild type and PPAR alpha-/- mice. Here we show that both enhancement of carnitine biosynthesis (due to increased gamma-butyrobetaine dioxygenase activity), extra-hepatic gamma-butyrobetaine synthesis and increased hepatic carnitine import (OCTN2 expression) contributes to the increased hepatic carnitine levels after fasting and that these processes are PPAR alpha-dependent

AB - In fasted rodents hepatic carnitine concentration increases considerably which is not observed in PPAR alpha-/- mice, indicating that PPAR alpha is involved in carnitine homeostasis. To investigate the mechanisms underlying the PPAR alpha-dependent hepatic carnitine accumulation we measured carnitine biosynthesis enzyme activities, levels of carnitine biosynthesis intermediates, acyl-carnitines and OCTN2 mRNA levels in tissues of untreated, fasted or Wy-14643-treated wild type and PPAR alpha-/- mice. Here we show that both enhancement of carnitine biosynthesis (due to increased gamma-butyrobetaine dioxygenase activity), extra-hepatic gamma-butyrobetaine synthesis and increased hepatic carnitine import (OCTN2 expression) contributes to the increased hepatic carnitine levels after fasting and that these processes are PPAR alpha-dependent

U2 - https://doi.org/10.1016/j.bbabio.2007.07.001

DO - https://doi.org/10.1016/j.bbabio.2007.07.001

M3 - Article

C2 - 17692817

SN - 0005-2728

VL - 1767

SP - 1134

EP - 1142

JO - BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS

JF - BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS

IS - 9

ER -