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

Abstract

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.—Fritzen, A. M., Lundsgaard, A.‐M., Jeppesen, J. F., Sjøberg, K. A., Høeg, L. D., Deleuran, H. H., Wojtaszewski, J. F. P., Richter, E. A., Kiens, B. Fatty acid type–specific regulation of SIRT1 does not affect insulin sensitivity in human skeletal muscle. FASEB J. 33, 5510–5519 (2019). http://www.fasebj.org

Small Amounts of Dietary Medium-Chain Fatty Acids Protect Against Insulin Resistance During Caloric Excess in Humans

“…The study was approved by the Copenhagen Ethics Committee (KF 01 261127). A few data from the LCSFA-HFD intervention have been published (26), as specified in the legend of table 1, figure 2 and 3.…”

Comparison of intramyocellular lipid metabolism in patients with diabetes and male athletes

“…2B. Next, we assessed the skeletal muscle saturated and unsaturated fatty acid turnover, which is represented by fractional incorporation rate of each, calculated after intravenous administration of [U 13 C]-palmitate (16.0) and [U 13 C]-linoleate (18.2 n-6) coupled with pre-and postinfusion skeletal muscle biopsies. Both palmitate and linoleate fractional incorporation rates were higher in athletes compared to patients with diabetes (0.62 ± 0.4 vs 0.15 ± 0.07%/h and 0.27 ± 0.1 vs 0.12 ± 0.06%/h respectively, a 4.1-fold for palmitate and 2.3-fold for linoleate) despite similar plasma rates of appearance, Table 3 and Fig.…”

“…The mean plasma TTR was based on samples taken from 2-4 h of infusion. The fractional incorporation rate (FIR) for skeletal muscle palmitate and linoleate was calculated using the following formula 56 : FIR (%/h) = (total 13 C at t 4total 13 C at t 0 ) * 1/(AUC plasma TTR * f 2 )*100, where t 4 = time of post-infusion biopsy (4 h) and t 0 is time of pre-infusion biopsy (background enrichment). The area under the curve (AUC) for plasma enrichments of each fatty acid was calculated by trapezoid analysis based on the ten time points for the m + 16 and m + 18 isotopomer enrichments, respectively.…”

“…The intervention was deconditioning for athletes and endurance exercise training for patients with type 2 diabetes, which influenced participants' basal insulin sensitivity status. At the distinct baseline and postintervention stages, we captured the skeletal muscle spectroscopic detection of saturated versus unsaturated carbon bonds contained within intramyocellular lipid stores, stable isotope [U- 13 C] turnover of skeletal muscle saturated and unsaturated fatty acids, lipidomic, metabolic, molecular and physical performance profiling. We characterised the skeletal muscle intramyocellular lipid signature of athletic health versus diabetes dysmetabolism.…”

Nutritional Therapy for Athletes with Diabetes

“…The current recommendation for people with diabetes establishes a protein intake not exceeding 15% of the total caloric intake [40], considering a daily assumption of 0.80-1 g/day per kg of body weight [41]. Fat content can differ from 30% to 50% of the total caloric intake [42], with polyunsaturated fatty acids (PUFA) ideally accounting for 10% [43]. Olive oil and fish oil consumption should be recommended, as they are considered a major source of monounsaturated fatty acids (MUFA) and omega 3 (ω-3) fatty acids, respectively [36].…”