Dataset Information

Polyunsaturated fatty acids acutely affect triacylglycerol-derived skeletal muscle fatty acid uptake and increases postprandial insulin sensitivity

ABSTRACT: Dietary fat quality may influence skeletal muscle lipid handling and fat accumulation, thereby modulating insulin sensitivity. Objective: To examine acute effects of meals with various fatty acid (FA) compositions on skeletal muscle FA handling and postprandial insulin sensitivity in obese insulin resistant men. Design: In a single-blinded randomized crossover study, 10 insulin resistant men consumed three high-fat mixed-meals (2.6MJ). Meals were high in saturated FA (SFA), in monounsaturated FA (MUFA) or in polyunsaturated FA (PUFA). Fasting and postprandial skeletal muscle FA handling were examined by measuring arterio-venous concentration differences across forearm muscle. [2H2]-palmitate was infused intravenously to label endogenous triacylglycerol (TAG) and FFA in the circulation and [U-13C]-palmitate was added to the meal to label chylomicron-TAG. Skeletal muscle biopsies were taken to assess intramuscular lipid metabolism and gene expression. Results: Insulin and glucose responses (AUC) after SFA meal were significantly higher compared with PUFA meal (p=0.003 and 0.028, respectively). Uptake of TAG-derived FA was significantly lower in the early postprandial phase after PUFA meal as compared with other meals (AUC60-120, p<0.001). The PUFA meal induced less transcriptional downregulation of oxidative pathways compared with other meals. The fractional synthetic rate was higher in DAG and PL fraction after MUFA and PUFA meal. Conclusion: Intake of a PUFA meal reduced TAG-derived skeletal muscle FA uptake, which was accompanied by higher postprandial insulin sensitivity and a tendency towards a higher muscle lipid turnover. These data suggest that the effects of replacement of SFA by PUFA may contribute to less muscle lipid uptake and may be therefore protective against the development of insulin resistance. Keywords: expression profiling by array

ORGANISM(S): Homo sapiens

PROVIDER: GSE31901 | GEO | 2012/02/21

SECONDARY ACCESSION(S): PRJNA145213

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Physical inactivity and western diet are the main factors leading to skeletal muscle (and whole-body) insulin resistance – a defect in insulin-mediated glucose uptake and metabolism – and associated metabolic diseases, such as obesity and type 2 diabetes mellitus (T2D). The study of the response to a mixed meal (normalized for body mass and/or basal metabolic rate) is of particular interest, as it simulates the physiological response to a typical (daily) single meal that depends on both the secretory function of the beta cells (insulin response) and the sensitivity of skeletal muscle signaling to insulin – variables, which markedly changing during development of insulin resistance and T2D. We aimed to compare the early transcriptomic response to a mixed meal normalized to body mass in skeletal muscle of healthy subjects and obese patients without (Ob) and with T2D (Ob+T2D). To investigate the early transcriptomic response we took biopsy samples from the vastus lateralis muscle prior to and 1 h after a meal. In the Ob+T2D group the average level and increase in C-peptide and insulin in the blood were comparable with healthy subjects that, apparently, is explained by dysfunction of the beta-cells induced by chronic T2D. At the same time, the Ob+T2D group demonstrated dysregulation of mixed meal-induced gene expression in skeletal muscle: morу than two times lower number of DEGs and a small overlapping with the gene response in the control group. On the contrary, the postprandial level of C-peptide and insulin in the Ob group was significantly greater than in healthy control that is related to insulin oversecretion associated with insulin resistance. Despite this, the gene response in skeletal muscle was also significantly dysregulated; moreover, it differed from the response in the Ob+T2D group. It means that defect in regulation of insulin-induced gene expression (insulin resistance in terms of gene expression) appears at the first stage of the development of metabolic disorders.

Project description:The obese, insulin resistant state is characterized by impairments in lipid metabolism. Dietary polyphenols might improve these deteriorations. We have previously shown that 3-days supplementation of combined Epigallocatechin-gallate and Resveratrol (E+R) increased energy expenditure, which was accompanied by improved metabolic flexibility after a high-fat mixed-meal (HFMM) in men. The present study aimed to investigate whether these short-term effects translate into longer-term improvement of insulin sensitivity and lipid metabolism. In this randomized, double-blind study, 42 overweight subjects (21 male, 38Â±2 yrs, BMI 29.7Â±0.5 kg/m2, HOMA-IR 2.1Â±0.2) received either E+R (300 and 80 mg/d, respectively) or placebo (PLA) for 12 weeks (3 months). Before (t0) and after (t3) intervention, tissue-specific insulin sensitivity was assessed by a hyperinsulinemic-euglycemic clamp with stable isotope infusion. Fasting and postprandial (HFMM) lipid metabolism was assessed using indirect calorimetry and blood sampling. Adipose tissue and skeletal muscle lipolysis was measured using microdialysis in men and skeletal muscle biopsies were collected to assess mitochondrial function and gene expression alterations via microarray analysis. E+R supplementation increased fasting (P=0.06) and postprandial (P=0.03) fat oxidation but did not alter energy expenditure compared to PLA. This was accompanied by an E+R-induced increase in oxidative capacity in permeabilized muscle fibers (p<0.05). Moreover, E+R supplementation attenuated the increase in plasma triacylglycerol concentration that was observed in the PLA group (AUC, p<0.05), and tended to decrease visceral fat mass (P=0.09). Finally, insulin-stimulated glucose disposal and suppression of endogenous glucose production were not affected by E+R supplementation. 12 weeks E+R supplementation increased whole-body fat oxidation and skeletal muscle oxidative capacity, but this did not translate into increased tissue-specific insulin sensitivity in overweight and obese subjects. To identify pathways that may underlie the E+R-induced improvement of skeletal muscle mitochondrial capacity, we performed microarray analysis on skeletal muscle biopsies (vastus lateralis muscle), collected before and after 12-weeks E+R or PLA treatment. Gene Set Enrichment Analysis (GSEA) indicated that the most upregulated pathways after E+R supplementation were related to the citric acid cycle and respiratory electron transport chain, while pathways related to carbohydrate metabolism were upregulated in the PLA group. In this randomized, double-blind placebo-controlled, parallel intervention trial, subjects received either a combination of E+R supplements (INTV, 282 mg/d and 80 mg/d, respectively) or placebo (PLA, partly hydrolyzed microcrystalline cellulose-filled capsules) for a period of 12 weeks (3 months) to assess effects of E+R supplementation on tissue-specific insulin sensitivity (primary outcomes) and fasting and postprandial substrate metabolism (secondary outcomes). Skeletal muscle (m. vastus lateralis) biopsies were taken under local anesthesia during fasting conditions before (t0) and after the 12-weeks (t3) intervention period. Extraxted RNA was hybridized on HTA 2.0 Affymetrix arrays and microarray analysis was performed on paired sample sets for 27 subjects (p, PLA n = 14; E+R n = 13).

Project description:Aims/hypothesis: While lipid deposition in skeletal muscle is considered to be involved in obesity-associated insulin resistance, neutral intramyocellular lipid (IMCL) accumulation per se does not necessarily induce insulin resistance. We previously demonstrated that overexpression of the lipid droplet coat protein perilipin 2 augments intramyocellular lipid content while improving insulin sensitivity. Another member of the perilipin family, perilipin 5 (PLIN5), is predominantly expressed in oxidative tissues like skeletal muscle. Here we investigated the effects of PLIN5 overexpression M-bM-^@M-^S in comparison with effects of PLIN2 M-bM-^@M-^S on skeletal muscle lipid levels, gene expression profiles and insulin sensitivity. Methods: Gene electroporation was used to overexpress PLIN5 in tibialis anterior muscle of rats fed a high fat diet. Eight days after electroporation, insulin-mediated glucose uptake in skeletal muscle was measured by means of a hyperinsulinemic euglycemic clamp. Electron microscopy, fluorescence microscopy and lipid extractions were performed to investigate IMCL accumulation. Gene expression profiles were obtained using microarrays. Results: TAG storage and lipid droplet size increased upon PLIN5 overexpression. Despite the higher IMCL content, insulin sensitivity was not impaired and DAG and acylcarnitine levels were unaffected. In contrast to the effects of PLIN2 overexpression, microarray data analysis revealed a gene expression profile favoring FA oxidation and improved mitochondrial function. Conclusions/interpretation: Both PLIN2 and PLIN5 increase neutral IMCL content without impeding insulin-mediated glucose uptake. As opposed to the effects of PLIN2 overexpression, overexpression of PLIN5 in skeletal muscle promoted expression of a cluster of genes under control of PPARM-NM-1 and PGC1M-NM-1 involved in FA catabolism and mitochondrial oxidation. Rats received a high fat diet for 3 weeks; 2 weeks after start of the diet intervention Plin5 (OXPAT) or Plin2 (ADRP) were overexpressed in either the right or left tibialis anterior muscle. One week later pooled tibialis anterior muscle samples were analysed on microarrays.

Dataset Information

Polyunsaturated fatty acids acutely affect triacylglycerol-derived skeletal muscle fatty acid uptake and increases postprandial insulin sensitivity

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets