Carnitine acetyltransferase: A new player in skeletal muscle insulin resistance?

Sofia Mikkelsen Berg, Henning Beck-Nielsen, Nils Joakim Færgeman*, Michael Gaster

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Resumé

Carnitine acetyltransferase (CRAT) deficiency has previously been shown to result in muscle insulin resistance due to accumulation of long-chain acylcarnitines. However, differences in the acylcarnitine profile and/or changes in gene expression and protein abundance of CRAT in myotubes obtained from obese patients with type 2 diabetes mellitus (T2DM) and glucose-tolerant obese and lean controls remain unclear. The objective of the study was to examine whether myotubes from obese patients with T2DM express differences in gene expression and protein abundance of CRAT and in acylcarnitine species pre-cultured under glucose and insulin concentrations similar to those observed in healthy individuals in the over-night fasted, resting state. Primary myotubes obtained from obese persons with or without T2DM and lean controls (n=9 in each group) were cultivated and harvested for LC-MS-based profiling of acylcarnitines. The mRNA expression and protein abundance of CRAT were determined by qPCR and Western Blotting, respectively. Our results suggest that the mRNA levels and protein abundance of CRAT were similar between groups. Of the 14 different acylcarnitine species measured by LC-MS, the levels of palmitoylcarnitine (C16) and octadecanoylcarnitine (C18) were slightly reduced in myotubes derived from T2DM patients (p<0.05) compared to glucose-tolerant obese and lean controls. This suggests that the CRAT function is not the major contributor to primary insulin resistance in cultured myotubes obtained from obese T2DM patients.

OriginalsprogEngelsk
TidsskriftBiochemistry and Biophysics Reports
Vol/bind9
Sider (fra-til)47-50
ISSN2405-5808
DOI
StatusUdgivet - 2017

Fingeraftryk

Carnitine O-Acetyltransferase
Type 2 Diabetes Mellitus
Muscle
Insulin Resistance
Medical problems
Skeletal Muscle
Insulin
Proteins
Gene expression
Glucose
Palmitoylcarnitine
Messenger RNA
acylcarnitine
Muscles

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title = "Carnitine acetyltransferase: A new player in skeletal muscle insulin resistance?",
abstract = "Carnitine acetyltransferase (CRAT) deficiency has previously been shown to result in muscle insulin resistance due to accumulation of long-chain acylcarnitines. However, differences in the acylcarnitine profile and/or changes in gene expression and protein abundance of CRAT in myotubes obtained from obese patients with type 2 diabetes mellitus (T2DM) and glucose-tolerant obese and lean controls remain unclear. The objective of the study was to examine whether myotubes from obese patients with T2DM express differences in gene expression and protein abundance of CRAT and in acylcarnitine species pre-cultured under glucose and insulin concentrations similar to those observed in healthy individuals in the over-night fasted, resting state. Primary myotubes obtained from obese persons with or without T2DM and lean controls (n=9 in each group) were cultivated and harvested for LC-MS-based profiling of acylcarnitines. The mRNA expression and protein abundance of CRAT were determined by qPCR and Western Blotting, respectively. Our results suggest that the mRNA levels and protein abundance of CRAT were similar between groups. Of the 14 different acylcarnitine species measured by LC-MS, the levels of palmitoylcarnitine (C16) and octadecanoylcarnitine (C18) were slightly reduced in myotubes derived from T2DM patients (p<0.05) compared to glucose-tolerant obese and lean controls. This suggests that the CRAT function is not the major contributor to primary insulin resistance in cultured myotubes obtained from obese T2DM patients.",
keywords = "Acylcarnitine, Carnitine acetyltransferase, Insulin, LC-MS, Myotubes, Resistance, Type 2 diabetes mellitus",
author = "Berg, {Sofia Mikkelsen} and Henning Beck-Nielsen and F{\ae}rgeman, {Nils Joakim} and Michael Gaster",
year = "2017",
doi = "10.1016/j.bbrep.2016.11.010",
language = "English",
volume = "9",
pages = "47--50",
journal = "Biochemistry and Biophysics Reports",
issn = "2405-5808",
publisher = "Elsevier",

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Carnitine acetyltransferase : A new player in skeletal muscle insulin resistance? / Berg, Sofia Mikkelsen; Beck-Nielsen, Henning; Færgeman, Nils Joakim; Gaster, Michael.

I: Biochemistry and Biophysics Reports , Bind 9, 2017, s. 47-50.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Carnitine acetyltransferase

T2 - A new player in skeletal muscle insulin resistance?

AU - Berg, Sofia Mikkelsen

AU - Beck-Nielsen, Henning

AU - Færgeman, Nils Joakim

AU - Gaster, Michael

PY - 2017

Y1 - 2017

N2 - Carnitine acetyltransferase (CRAT) deficiency has previously been shown to result in muscle insulin resistance due to accumulation of long-chain acylcarnitines. However, differences in the acylcarnitine profile and/or changes in gene expression and protein abundance of CRAT in myotubes obtained from obese patients with type 2 diabetes mellitus (T2DM) and glucose-tolerant obese and lean controls remain unclear. The objective of the study was to examine whether myotubes from obese patients with T2DM express differences in gene expression and protein abundance of CRAT and in acylcarnitine species pre-cultured under glucose and insulin concentrations similar to those observed in healthy individuals in the over-night fasted, resting state. Primary myotubes obtained from obese persons with or without T2DM and lean controls (n=9 in each group) were cultivated and harvested for LC-MS-based profiling of acylcarnitines. The mRNA expression and protein abundance of CRAT were determined by qPCR and Western Blotting, respectively. Our results suggest that the mRNA levels and protein abundance of CRAT were similar between groups. Of the 14 different acylcarnitine species measured by LC-MS, the levels of palmitoylcarnitine (C16) and octadecanoylcarnitine (C18) were slightly reduced in myotubes derived from T2DM patients (p<0.05) compared to glucose-tolerant obese and lean controls. This suggests that the CRAT function is not the major contributor to primary insulin resistance in cultured myotubes obtained from obese T2DM patients.

AB - Carnitine acetyltransferase (CRAT) deficiency has previously been shown to result in muscle insulin resistance due to accumulation of long-chain acylcarnitines. However, differences in the acylcarnitine profile and/or changes in gene expression and protein abundance of CRAT in myotubes obtained from obese patients with type 2 diabetes mellitus (T2DM) and glucose-tolerant obese and lean controls remain unclear. The objective of the study was to examine whether myotubes from obese patients with T2DM express differences in gene expression and protein abundance of CRAT and in acylcarnitine species pre-cultured under glucose and insulin concentrations similar to those observed in healthy individuals in the over-night fasted, resting state. Primary myotubes obtained from obese persons with or without T2DM and lean controls (n=9 in each group) were cultivated and harvested for LC-MS-based profiling of acylcarnitines. The mRNA expression and protein abundance of CRAT were determined by qPCR and Western Blotting, respectively. Our results suggest that the mRNA levels and protein abundance of CRAT were similar between groups. Of the 14 different acylcarnitine species measured by LC-MS, the levels of palmitoylcarnitine (C16) and octadecanoylcarnitine (C18) were slightly reduced in myotubes derived from T2DM patients (p<0.05) compared to glucose-tolerant obese and lean controls. This suggests that the CRAT function is not the major contributor to primary insulin resistance in cultured myotubes obtained from obese T2DM patients.

KW - Acylcarnitine

KW - Carnitine acetyltransferase

KW - Insulin

KW - LC-MS

KW - Myotubes

KW - Resistance

KW - Type 2 diabetes mellitus

U2 - 10.1016/j.bbrep.2016.11.010

DO - 10.1016/j.bbrep.2016.11.010

M3 - Journal article

C2 - 28955988

AN - SCOPUS:84997606070

VL - 9

SP - 47

EP - 50

JO - Biochemistry and Biophysics Reports

JF - Biochemistry and Biophysics Reports

SN - 2405-5808

ER -