The RabGAPs TBC1D1 and TBC1D4 Control Uptake of Long-Chain Fatty Acids Into Skeletal Muscle via Fatty Acid Transporter SLC27A4/FATP4.


Journal

Diabetes
ISSN: 1939-327X
Titre abrégé: Diabetes
Pays: United States
ID NLM: 0372763

Informations de publication

Date de publication:
11 2020
Historique:
received: 20 02 2020
accepted: 24 08 2020
pubmed: 2 9 2020
medline: 26 1 2021
entrez: 2 9 2020
Statut: ppublish

Résumé

The two closely related RabGTPase-activating proteins (RabGAPs) TBC1D1 and TBC1D4 play a crucial role in the regulation of GLUT4 translocation in response to insulin and contraction in skeletal muscle. In mice, deficiency in one or both RabGAPs leads to reduced insulin- and contraction-stimulated glucose uptake and to elevated fatty acid (FA) uptake and oxidation in both glycolytic and oxidative muscle fibers without altering mitochondrial copy number and the abundance of proteins for oxidative phosphorylation. Here we present evidence for a novel mechanism of skeletal muscle lipid utilization involving the two RabGAPs and the FA transporter SLC27A4/FATP4. Both RabGAPs control the uptake of saturated and unsaturated long-chain FAs (LCFAs) into skeletal muscle and knockdown (Kd) of a subset of RabGAP substrates,

Identifiants

pubmed: 32868338
pii: db20-0180
doi: 10.2337/db20-0180
doi:

Substances chimiques

Fatty Acid Transport Proteins 0
Fatty Acids 0
GTPase-Activating Proteins 0
Slc27a4 protein, mouse 0
Tbc1d1 protein, mouse 0
Tbc1d4 protein, mouse 0

Banques de données

figshare
['10.2337/figshare.12857771']

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2281-2293

Informations de copyright

© 2020 by the American Diabetes Association.

Auteurs

Tim Benninghoff (T)

Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Duesseldorf, Medical Faculty, Duesseldorf, Germany.
German Center for Diabetes Research, München-Neuherberg, Germany.

Lena Espelage (L)

Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Duesseldorf, Medical Faculty, Duesseldorf, Germany.
German Center for Diabetes Research, München-Neuherberg, Germany.

Samaneh Eickelschulte (S)

Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Duesseldorf, Medical Faculty, Duesseldorf, Germany.
German Center for Diabetes Research, München-Neuherberg, Germany.

Isabel Zeinert (I)

Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Duesseldorf, Medical Faculty, Duesseldorf, Germany.

Isabelle Sinowenka (I)

Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Duesseldorf, Medical Faculty, Duesseldorf, Germany.

Frank Müller (F)

Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Duesseldorf, Medical Faculty, Duesseldorf, Germany.

Christina Schöndeling (C)

Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Duesseldorf, Medical Faculty, Duesseldorf, Germany.

Hannah Batchelor (H)

Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Duesseldorf, Medical Faculty, Duesseldorf, Germany.

Sandra Cames (S)

Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Duesseldorf, Medical Faculty, Duesseldorf, Germany.
German Center for Diabetes Research, München-Neuherberg, Germany.

Zhou Zhou (Z)

Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Duesseldorf, Medical Faculty, Duesseldorf, Germany.

Jörg Kotzka (J)

Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Duesseldorf, Medical Faculty, Duesseldorf, Germany.
German Center for Diabetes Research, München-Neuherberg, Germany.

Alexandra Chadt (A)

Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Duesseldorf, Medical Faculty, Duesseldorf, Germany alexandra.chadt@ddz.de.
German Center for Diabetes Research, München-Neuherberg, Germany.

Hadi Al-Hasani (H)

Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Duesseldorf, Medical Faculty, Duesseldorf, Germany.
German Center for Diabetes Research, München-Neuherberg, Germany.

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Classifications MeSH