Fatty acid type-specific regulation of SIRT1 does not affect insulin sensitivity in human skeletal muscle

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

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

SN - 0892-6638

VL - 33

SP - 5510

EP - 5519

JO - F A S E B Journal

JF - F A S E B Journal

IS - 4

ER -