Fatty Acid Incubation of Myotubues from Humans with Type 2 Diabetes Leads to Enhanced Release of Beta Oxidation Products Due to Impaired Fatty Acid Oxidation

 Effects of Tetradecylthioacetic Acid and Eicosapentaenoic Acid

Andreas J Wensaas, Arild C Rustan, Marlene Just, Rolf K Berge, Christian A Drevon, Michael Gaster

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Udgivelsesdato: 2008-Dec-9
OriginalsprogEngelsk
TidsskriftDiabetes
ISSN0046-0192
DOI
StatusUdgivet - 9. dec. 2008

Fingeraftryk

Eicosapentaenoic Acid
Type 2 Diabetes Mellitus
Fatty Acids
Palmitic Acid
Lipids
1-(carboxymethylthio)tetradecane
Insulin Resistance
Lactic Acid
Skeletal Muscle
Research Design

Citer dette

@article{6b99b6a0d67011dd9908000ea68e967b,
title = "Fatty Acid Incubation of Myotubues from Humans with Type 2 Diabetes Leads to Enhanced Release of Beta Oxidation Products Due to Impaired Fatty Acid Oxidation:  Effects of Tetradecylthioacetic Acid and Eicosapentaenoic Acid",
abstract = "Objective: Increased availability of fatty acids is important for accumulation of intracellular lipids and development of insulin resistance in human myotubes. It is unknown whether different types of fatty acids like eicosapentaenoic acid (EPA) or tetradecylthioacetic acid (TTA) influence these processes. Research Design and Methods: We examined fatty acid and glucose metabolism, and gene expression in cultured human skeletal muscle cells from control and T2D individuals after four days preincubation with EPA or TTA. Results: T2D myotubes exhibited reduced formation of CO(2) from palmitic acid (PA), whereas release of beta-oxidation products was unchanged at baseline, but significantly increased with respect to control myotubes after preincubation with TTA and EPA. Preincubation with TTA enhanced both complete (CO(2)) and beta-oxidation of PA, whereas EPA increased only beta-oxidation significantly. EPA markedly enhanced TAG accumulation in myotubes, more pronounced in T2D cells. TAG accumulation and fatty acid oxidation were inversely correlated only after EPA preincubation, and total level of acyl-CoA was reduced. Glucose oxidation (CO(2) formation) was enhanced and lactate production decreased after chronic exposure to EPA and TTA, whereas glucose uptake and storage were unchanged. Both EPA and especially TTA increased the expression of genes involved in fatty acid uptake, activation, accumulation and oxidation. Conclusion: Our results suggest: a) mitochondrial dysfunction in diabetic myotubes is caused by disturbances downstream of fatty acid beta-oxidation; b) EPA promoted accumulation of TAG, enhanced beta-oxidation and increased glucose oxidation; c) TTA improved complete PA oxidation in diabetic myotubes, opposed increased lipid accumulation and increased glucose oxidation.",
author = "Wensaas, {Andreas J} and Rustan, {Arild C} and Marlene Just and Berge, {Rolf K} and Drevon, {Christian A} and Michael Gaster",
year = "2008",
month = "12",
day = "9",
doi = "10.2337/db08-1043",
language = "English",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",

}

Fatty Acid Incubation of Myotubues from Humans with Type 2 Diabetes Leads to Enhanced Release of Beta Oxidation Products Due to Impaired Fatty Acid Oxidation :  Effects of Tetradecylthioacetic Acid and Eicosapentaenoic Acid. / Wensaas, Andreas J; Rustan, Arild C; Just, Marlene; Berge, Rolf K; Drevon, Christian A; Gaster, Michael.

I: Diabetes, 09.12.2008.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Fatty Acid Incubation of Myotubues from Humans with Type 2 Diabetes Leads to Enhanced Release of Beta Oxidation Products Due to Impaired Fatty Acid Oxidation

T2 -  Effects of Tetradecylthioacetic Acid and Eicosapentaenoic Acid

AU - Wensaas, Andreas J

AU - Rustan, Arild C

AU - Just, Marlene

AU - Berge, Rolf K

AU - Drevon, Christian A

AU - Gaster, Michael

PY - 2008/12/9

Y1 - 2008/12/9

N2 - Objective: Increased availability of fatty acids is important for accumulation of intracellular lipids and development of insulin resistance in human myotubes. It is unknown whether different types of fatty acids like eicosapentaenoic acid (EPA) or tetradecylthioacetic acid (TTA) influence these processes. Research Design and Methods: We examined fatty acid and glucose metabolism, and gene expression in cultured human skeletal muscle cells from control and T2D individuals after four days preincubation with EPA or TTA. Results: T2D myotubes exhibited reduced formation of CO(2) from palmitic acid (PA), whereas release of beta-oxidation products was unchanged at baseline, but significantly increased with respect to control myotubes after preincubation with TTA and EPA. Preincubation with TTA enhanced both complete (CO(2)) and beta-oxidation of PA, whereas EPA increased only beta-oxidation significantly. EPA markedly enhanced TAG accumulation in myotubes, more pronounced in T2D cells. TAG accumulation and fatty acid oxidation were inversely correlated only after EPA preincubation, and total level of acyl-CoA was reduced. Glucose oxidation (CO(2) formation) was enhanced and lactate production decreased after chronic exposure to EPA and TTA, whereas glucose uptake and storage were unchanged. Both EPA and especially TTA increased the expression of genes involved in fatty acid uptake, activation, accumulation and oxidation. Conclusion: Our results suggest: a) mitochondrial dysfunction in diabetic myotubes is caused by disturbances downstream of fatty acid beta-oxidation; b) EPA promoted accumulation of TAG, enhanced beta-oxidation and increased glucose oxidation; c) TTA improved complete PA oxidation in diabetic myotubes, opposed increased lipid accumulation and increased glucose oxidation.

AB - Objective: Increased availability of fatty acids is important for accumulation of intracellular lipids and development of insulin resistance in human myotubes. It is unknown whether different types of fatty acids like eicosapentaenoic acid (EPA) or tetradecylthioacetic acid (TTA) influence these processes. Research Design and Methods: We examined fatty acid and glucose metabolism, and gene expression in cultured human skeletal muscle cells from control and T2D individuals after four days preincubation with EPA or TTA. Results: T2D myotubes exhibited reduced formation of CO(2) from palmitic acid (PA), whereas release of beta-oxidation products was unchanged at baseline, but significantly increased with respect to control myotubes after preincubation with TTA and EPA. Preincubation with TTA enhanced both complete (CO(2)) and beta-oxidation of PA, whereas EPA increased only beta-oxidation significantly. EPA markedly enhanced TAG accumulation in myotubes, more pronounced in T2D cells. TAG accumulation and fatty acid oxidation were inversely correlated only after EPA preincubation, and total level of acyl-CoA was reduced. Glucose oxidation (CO(2) formation) was enhanced and lactate production decreased after chronic exposure to EPA and TTA, whereas glucose uptake and storage were unchanged. Both EPA and especially TTA increased the expression of genes involved in fatty acid uptake, activation, accumulation and oxidation. Conclusion: Our results suggest: a) mitochondrial dysfunction in diabetic myotubes is caused by disturbances downstream of fatty acid beta-oxidation; b) EPA promoted accumulation of TAG, enhanced beta-oxidation and increased glucose oxidation; c) TTA improved complete PA oxidation in diabetic myotubes, opposed increased lipid accumulation and increased glucose oxidation.

U2 - 10.2337/db08-1043

DO - 10.2337/db08-1043

M3 - Journal article

JO - Diabetes

JF - Diabetes

SN - 0012-1797

ER -