Acylcarnitines

Schooneman, Marieke G.; Vaz, Frédéric M.; Houten, Sander M.; Soeters, Maarten R.

doi:10.2337/db12-0466

Cited by 616Lipid metabolism and biosynthesisMetabolism and Genetic DisordersDiabetes, Cardiovascular Risks, and Lipoproteins

Acylcarnitines

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Schooneman, Marieke G., Vaz, Frédéric M., Houten, Sander M., Soeters, Maarten R.·2013·Diabetes

DOI 10.2337/db12-0466PMC PMC3526046

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Abstract

The incidence of obesity and insulin resistance is growing, and the increase in type 2 diabetes mellitus (DM2) constitutes one of the biggest challenges for our healthcare systems. Many theories are proposed for the induction of insulin resistance in glucose and lipid metabolism and its metabolic sequelae. One of these mechanisms is lipotoxicity (1–4): excess lipid supply and subsequent lipid accumulation in insulin-sensitive tissues such as skeletal muscle interfere with insulin-responsive metabolic pathways. Various lipid intermediates, like ceramides, gangliosides, diacylglycerol, and other metabolites, have been held responsible for insulin resistance (2,3,5–10). These intermediates can exert such effects because they are signaling molecules and building blocks of cellular membranes, which harbor the insulin receptor. In addition, lipids play an important role in energy homeostasis. Fatty acids (FA) can be metabolized via mitochondrial FA oxidation (FAO), which yields energy (11). As such, FAO competes with glucose oxidation in a process known as the glucose-FA, or Randle, cycle (12). Muoio and colleagues (1,13,14) proposed an alternative mechanism in which FAO rate outpaces the tricarboxylic acid cycle (TCA), thereby leading to the accumulation of intermediary metabolites such as acylcarnitines that may interfere with insulin sensitivity. This accumulation of acylcarnitines corroborates with some human studies showing that acylcarnitines are associated with insulin resistance (15–17). In addition, acylcarnitines have a long history in the diagnosis and neonatal screening of FAO defects and other inborn errors of metabolism (18). This knowledge may aid to understand the interaction between FAO and insulin resistance and fuel future research. In this review, we discuss the role of acylcarnitines in FAO and insulin resistance as emerging from animal and human studies. ### Carnitine biosynthesis and regulation of tissue carnitine content. To guarantee continuous energy supply, the human body oxidizes considerable amounts of fat besides glucose. …

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In obese individuals, impaired mitochondrial function might contribute to lower intramyocellular lipid turnover and lead to lipotoxicity.
“In obese individuals, impaired mitochondrial function might contribute to lower IMCL turnover and lead to lipotoxicity (Schooneman et al, 2013).”
From Mitochondrial response to nutrient availability and its role in metabolic disease (2014) · cites this paper as Schooneman et al, 2013
Lipid accumulation in non-adipose tissues is highly associated with insulin resistance.
“but lipid accumulation in non-adipose tissues is also highly associated with insulin resistance (Canto & Auwerx, 2009; Corpeleijn et al, 2009; Schooneman et al, 2013).”
From Mitochondrial response to nutrient availability and its role in metabolic disease (2014) · cites this paper as Schooneman et al, 2013

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[20]van Vlies N Ferdinandusse S Wanders RJA Vaz FM PPARalfa-activation results in enhanced carnitine biosynthesis and OCTN2 expression. Biochim Biophys Acta 1767; 11: 2007 17692817

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Authors: Schooneman, M. G., Vaz, F. M., Houten, S. M., & Soeters, M. R.
Affiliations: Amsterdam UMC Location University of Amsterdam (NL)
Corresponding author: Soeters, Maarten R.
ORCID: Schooneman, Marieke G.
Vaz, Frédéric M.
Houten, Sander M.
Soeters, Maarten R.
Venue: Diabetes
Publisher: American Diabetes Association
Published: 2012-12-13
Volume: 62
Issue: 1
Pages: 1-8
ISSN: 0012-1797 (ISSN-L)
1939-327X
DOI: 10.2337/db12-0466
PMC: PMC3526046
OpenAlex: W2037136746
Cited by: 616
References: 80
Citations by year: 2026: 36 · 2025: 40 · 2024: 35 · 2023: 49 · 2022: 60 · 2021: 89 · 2020: 61 · 2019: 54 · 2018: 57 · 2017: 33 · 2016: 42 · 2015: 29 · 2014: 25 · 2013: 5
FWCI: 1.55
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-nd
creativecommons.org/licenses/by-nc-nd/3.0/ (vor, 3179 d)
Locations: Diabetes (publishedVersion, cc-by-nc-nd)
PubMed Central (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
Pure Amsterdam UMC (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords: acylcarnitines, insulin resistance, type 2 diabetes, fatty acid oxidation, lipotoxicity, carnitine biosynthesis, Randle cycle, mitochondrial bioenergetics, skeletal muscle, inborn errors of metabolism, newborn screening
MeSH terms: Animals, Carnitine, Citric Acid Cycle, Fatty Acids, Humans, Insulin Resistance, Oxidation-Reduction, Lipid Metabolism

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