Fatty acid type-specific regulation of SIRT1 does not affect insulin sensitivity in human skeletal muscle
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Fatty acid type-specific regulation of SIRT1 does not affect insulin sensitivity in human skeletal muscle. / Fritzen, Andreas Mæchel; Lundsgaard, Annemarie; Jeppesen, Jacob Fuglsbjerg; Sjøberg, Kim Anker; Høeg, Louise Dalgas; Deleuran, Henrik Hall; Wojtaszewski, Jørgen; Richter, Erik A.; Kiens, Bente.
In: F A S E B Journal, Vol. 33, No. 4, 2019, p. 5510-5519.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Fatty acid type-specific regulation of SIRT1 does not affect insulin sensitivity in human skeletal muscle
AU - Fritzen, Andreas Mæchel
AU - Lundsgaard, Annemarie
AU - Jeppesen, Jacob Fuglsbjerg
AU - Sjøberg, Kim Anker
AU - Høeg, Louise Dalgas
AU - Deleuran, Henrik Hall
AU - Wojtaszewski, Jørgen
AU - Richter, Erik A.
AU - Kiens, Bente
N1 - CURIS 2019 NEXS 040
PY - 2019
Y1 - 2019
N2 - The nicotinamide adenine dinucleotide-dependent deacetylase, sirtuin (SIRT)1, in skeletal muscle is reduced in insulin-resistant states. However, whether this is an initial mechanism responsible for mediating insulin resistance in human skeletal muscle remains to be investigated. Also, SIRT1 acts as a mitochondrial gene transcriptional regulator and is induced by a short-term, high-fat diet (HFD) in human skeletal muscle. Whether saturated or unsaturated fatty acids (FAs) in the diet are important for this is unknown. We subjected 17 healthy, young men to a eucaloric control (Con) diet and 1 of 2 hypercaloric [+75% energy (E%)] HFDs for 3 d enriched in either saturated (Sat) FA (79 E% fat; Sat) or unsaturated FA (78 E% fat; Unsat). After Sat, SIRT1 protein content and activity in skeletal muscle increased ( P < 0.05; ∼40%) while remaining unchanged after Unsat. Whole-body insulin sensitivity and insulin-stimulated leg glucose uptake were reduced ( P < 0.01; ∼20%) to a similar extent compared to Con after both HFDs. We demonstrate a novel FA type-dependent regulation of SIRT1 protein in human skeletal muscle. Moreover, regulation of SIRT1 does not seem to be an initiating factor responsible for mediating insulin resistance in human skeletal muscle.
AB - The nicotinamide adenine dinucleotide-dependent deacetylase, sirtuin (SIRT)1, in skeletal muscle is reduced in insulin-resistant states. However, whether this is an initial mechanism responsible for mediating insulin resistance in human skeletal muscle remains to be investigated. Also, SIRT1 acts as a mitochondrial gene transcriptional regulator and is induced by a short-term, high-fat diet (HFD) in human skeletal muscle. Whether saturated or unsaturated fatty acids (FAs) in the diet are important for this is unknown. We subjected 17 healthy, young men to a eucaloric control (Con) diet and 1 of 2 hypercaloric [+75% energy (E%)] HFDs for 3 d enriched in either saturated (Sat) FA (79 E% fat; Sat) or unsaturated FA (78 E% fat; Unsat). After Sat, SIRT1 protein content and activity in skeletal muscle increased ( P < 0.05; ∼40%) while remaining unchanged after Unsat. Whole-body insulin sensitivity and insulin-stimulated leg glucose uptake were reduced ( P < 0.01; ∼20%) to a similar extent compared to Con after both HFDs. We demonstrate a novel FA type-dependent regulation of SIRT1 protein in human skeletal muscle. Moreover, regulation of SIRT1 does not seem to be an initiating factor responsible for mediating insulin resistance in human skeletal muscle.
KW - Faculty of Science
KW - Sirtuins
KW - Nutrition
KW - Lipid metabolism
KW - NAD
U2 - 10.1096/fj.201801950R
DO - 10.1096/fj.201801950R
M3 - Journal article
C2 - 30707625
VL - 33
SP - 5510
EP - 5519
JO - F A S E B Journal
JF - F A S E B Journal
SN - 0892-6638
IS - 4
ER -
ID: 212909742