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Transcriptional metabolic inflexibility in skeletal muscle among individuals with increasing insulin resistance.
Obesity (Silver Spring). 2011 Nov; 19(11):2158-66.O

Abstract

Disturbances in skeletal muscle lipid metabolism may play an important role in development of insulin resistance (IR). The aim was to investigate transcriptional control of skeletal muscle fatty acid (FA) metabolism in individuals with the metabolic syndrome (MetS) with varying degrees of insulin sensitivity (S(I)). 122 individuals with MetS (NCEP-ATP III criteria) at age 35-70 years, BMI 27-38 kg/m(2) were studied (subgroup EU-LIPGENE study). Individuals were divided into quartiles of S(I) measured during a frequently sampled insulin modified intravenous glucose tolerance test. Skeletal muscle normalized mRNA expression levels of genes important in skeletal muscle FA handling were analyzed with quantitative real-time PCR. The expression of sterol regulatory element binding protein 1c (SREBP1c), acetyl-CoA carboxylase 2 (ACC2), diacylglycerol acyltransferase (DGAT1), and nuclear respiration factor (NRF) was higher in the lowest two quartiles of S(I) (<50th) compared with the highest two quartiles of S(I) (>50th). Interestingly, peroxisome proliferator-activated receptor coactivator 1α (PGC1α), peroxisome proliferator-activated receptor α (PPARα), and muscle carnitine palmitoyl transferase 1b (mCPT1), important for oxidative metabolism, showed a complex mRNA expression profile; levels were lower in both the most "insulin sensitive" (IS) as well as the most "IR" individuals. Lipoprotein lipase (LPL) mRNA was reduced in the lowest quartile of S(I). Enhanced gene expression of SREBP1c and ACC2 in the IR state suggests a tendency towards FA storage rather than oxidation. From the lower expression of PGC1α, PPARα, and mCPT1 in both the most "IS" as well as the most "IR" individuals, it may be speculated that "IS" subjects do not need to upregulate these genes to have a normal FA oxidation, whereas the most "IR" individuals are inflexible in upregulating these genes.

Authors+Show Affiliations

Department of Human Biology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre +, Maastricht, The Netherlands. anneke.jans@maastrichtuniversity.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21701566

Citation

Jans, Anneke, et al. "Transcriptional Metabolic Inflexibility in Skeletal Muscle Among Individuals With Increasing Insulin Resistance." Obesity (Silver Spring, Md.), vol. 19, no. 11, 2011, pp. 2158-66.
Jans A, Sparks LM, van Hees AM, et al. Transcriptional metabolic inflexibility in skeletal muscle among individuals with increasing insulin resistance. Obesity (Silver Spring). 2011;19(11):2158-66.
Jans, A., Sparks, L. M., van Hees, A. M., Gjelstad, I. M., Tierney, A. C., Risérus, U., Drevon, C. A., Roche, H. M., Schrauwen, P., & Blaak, E. E. (2011). Transcriptional metabolic inflexibility in skeletal muscle among individuals with increasing insulin resistance. Obesity (Silver Spring, Md.), 19(11), 2158-66. https://doi.org/10.1038/oby.2011.149
Jans A, et al. Transcriptional Metabolic Inflexibility in Skeletal Muscle Among Individuals With Increasing Insulin Resistance. Obesity (Silver Spring). 2011;19(11):2158-66. PubMed PMID: 21701566.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transcriptional metabolic inflexibility in skeletal muscle among individuals with increasing insulin resistance. AU - Jans,Anneke, AU - Sparks,Lauren M, AU - van Hees,Anneke M J, AU - Gjelstad,Ingrid M F, AU - Tierney,Audrey C, AU - Risérus,Ulf, AU - Drevon,Christian A, AU - Roche,Helen M, AU - Schrauwen,Patrick, AU - Blaak,Ellen E, Y1 - 2011/06/23/ PY - 2011/6/25/entrez PY - 2011/6/28/pubmed PY - 2012/3/1/medline SP - 2158 EP - 66 JF - Obesity (Silver Spring, Md.) JO - Obesity (Silver Spring) VL - 19 IS - 11 N2 - Disturbances in skeletal muscle lipid metabolism may play an important role in development of insulin resistance (IR). The aim was to investigate transcriptional control of skeletal muscle fatty acid (FA) metabolism in individuals with the metabolic syndrome (MetS) with varying degrees of insulin sensitivity (S(I)). 122 individuals with MetS (NCEP-ATP III criteria) at age 35-70 years, BMI 27-38 kg/m(2) were studied (subgroup EU-LIPGENE study). Individuals were divided into quartiles of S(I) measured during a frequently sampled insulin modified intravenous glucose tolerance test. Skeletal muscle normalized mRNA expression levels of genes important in skeletal muscle FA handling were analyzed with quantitative real-time PCR. The expression of sterol regulatory element binding protein 1c (SREBP1c), acetyl-CoA carboxylase 2 (ACC2), diacylglycerol acyltransferase (DGAT1), and nuclear respiration factor (NRF) was higher in the lowest two quartiles of S(I) (<50th) compared with the highest two quartiles of S(I) (>50th). Interestingly, peroxisome proliferator-activated receptor coactivator 1α (PGC1α), peroxisome proliferator-activated receptor α (PPARα), and muscle carnitine palmitoyl transferase 1b (mCPT1), important for oxidative metabolism, showed a complex mRNA expression profile; levels were lower in both the most "insulin sensitive" (IS) as well as the most "IR" individuals. Lipoprotein lipase (LPL) mRNA was reduced in the lowest quartile of S(I). Enhanced gene expression of SREBP1c and ACC2 in the IR state suggests a tendency towards FA storage rather than oxidation. From the lower expression of PGC1α, PPARα, and mCPT1 in both the most "IS" as well as the most "IR" individuals, it may be speculated that "IS" subjects do not need to upregulate these genes to have a normal FA oxidation, whereas the most "IR" individuals are inflexible in upregulating these genes. SN - 1930-739X UR - https://www.unboundmedicine.com/medline/citation/21701566/Transcriptional_metabolic_inflexibility_in_skeletal_muscle_among_individuals_with_increasing_insulin_resistance_ L2 - https://doi.org/10.1038/oby.2011.149 DB - PRIME DP - Unbound Medicine ER -