Relationship between insulin sensitivity and gene expression in human skeletal muscle

Abstract BackgroundInsulin resistance in skeletal muscle is a key feature of the pre-diabetic state, hypertension, dyslipidemia, cardiovascular diseases, and also predicts type 2 diabetes. However, the underlying molecular mechanisms are still poorly understood. MethodsTo explore these mechanisms, we related global skeletal muscle gene expression profiling of 38 non-diabetic men to physiological measures of insulin sensitivity. Results We identified 70 genes positively and 110 genes inversely correlated with insulin sensitivity in human skeletal muscle, identifying autophagy-related genes as positively correlated with insulin sensitivity. Replication in an independent study of 9 non-diabetic men resulted in 10 overlapping genes that strongly correlated with insulin sensitivity, including CPT1B and SIRT2 , involved in lipid metabolism, and FBXW5 that regulates mammalian target-of-rapamycin (mTOR) and autophagy. The expression of CPT1B , SIRT2 and FBXW5 was also positively correlated with the expression of key genes promoting the phenotype of an insulin sensitive myocyte e.g. PPARGC1A . ConclusionsThese data suggest that activation of genes involved in lipid metabolism, e.g. CPT1B and SIRT2 , and genes regulating autophagy and mTOR signaling, e.g. FBXW5 , are associated with increased insulin sensitivity in human skeletal muscle, reflecting a highly flexible nutrient sensing.

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Relationship between insulin sensitivity and gene expression in human skeletal muscle

10.21203/rs.3.rs-42125/v2 ◽

2020 ◽

Author(s):

Hemang Parikh ◽

Targ Elgzyri ◽

Amra Alibegovic ◽

Natalie Hiscock ◽

Ola Ekström ◽

...

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Skeletal Muscle ◽

Lipid Metabolism ◽

Insulin Sensitivity ◽

Human Skeletal Muscle ◽

Molecular Mechanisms ◽

Independent Study ◽

Nutrient Sensing ◽

Model Assessment

Abstract Background: Insulin resistance in skeletal muscle is a key feature of the pre-diabetic state, hypertension, dyslipidemia, cardiovascular diseases and also predicts type 2 diabetes. However, the underlying molecular mechanisms are still poorly understood. Methods: To explore these mechanisms, we related global skeletal muscle gene expression profiling of 38 non-diabetic men to a surrogate measure of insulin sensitivity, i.e. homeostatic model assessment of insulin resistance (HOMA-IR). Results: We identified 70 genes positively and 110 genes inversely correlated with insulin sensitivity in human skeletal muscle, identifying autophagy-related genes as positively correlated with insulin sensitivity. Replication in an independent study of 9 non-diabetic men resulted in 10 overlapping genes that strongly correlated with insulin sensitivity, including SIRT2, involved in lipid metabolism, and FBXW5 that regulates mammalian target-of-rapamycin (mTOR) and autophagy. The expressions of SIRT2 and FBXW5 were also positively correlated with the expression of key genes promoting the phenotype of an insulin sensitive myocyte e.g. PPARGC1A. Conclusions: These data suggest that activation of genes involved in lipid metabolism, e.g. SIRT2, and genes regulating autophagy and mTOR signaling, e.g. FBXW5, are associated with increased insulin sensitivity in human skeletal muscle, reflecting a highly flexible nutrient sensing.

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Relationship between insulin sensitivity and gene expression in human skeletal muscle

BMC Endocrine Disorders ◽

10.1186/s12902-021-00687-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Hemang M. Parikh ◽

Targ Elgzyri ◽

Amra Alibegovic ◽

Natalie Hiscock ◽

Ola Ekström ◽

...

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Skeletal Muscle ◽

Lipid Metabolism ◽

Insulin Sensitivity ◽

Human Skeletal Muscle ◽

Molecular Mechanisms ◽

Independent Study ◽

Nutrient Sensing ◽

Model Assessment

Abstract Background Insulin resistance (IR) in skeletal muscle is a key feature of the pre-diabetic state, hypertension, dyslipidemia, cardiovascular diseases and also predicts type 2 diabetes. However, the underlying molecular mechanisms are still poorly understood. Methods To explore these mechanisms, we related global skeletal muscle gene expression profiling of 38 non-diabetic men to a surrogate measure of insulin sensitivity, i.e. homeostatic model assessment of insulin resistance (HOMA-IR). Results We identified 70 genes positively and 110 genes inversely correlated with insulin sensitivity in human skeletal muscle, identifying autophagy-related genes as positively correlated with insulin sensitivity. Replication in an independent study of 9 non-diabetic men resulted in 10 overlapping genes that strongly correlated with insulin sensitivity, including SIRT2, involved in lipid metabolism, and FBXW5 that regulates mammalian target-of-rapamycin (mTOR) and autophagy. The expressions of SIRT2 and FBXW5 were also positively correlated with the expression of key genes promoting the phenotype of an insulin sensitive myocyte e.g.PPARGC1A. Conclusions The muscle expression of 180 genes were correlated with insulin sensitivity. These data suggest that activation of genes involved in lipid metabolism, e.g.SIRT2, and genes regulating autophagy and mTOR signaling, e.g.FBXW5, are associated with increased insulin sensitivity in human skeletal muscle, reflecting a highly flexible nutrient sensing.

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SGDB: A Sports Gene Database for Visualization of Sports Effects on Human Skeletal Muscle Gene Expression

IEEE Access ◽

10.1109/access.2020.2968514 ◽

2020 ◽

Vol 8 ◽

pp. 20557-20562 ◽

Cited By ~ 3

Author(s):

Qinglei Cao ◽

Zhongyuan Deng ◽

Juan Liu ◽

Xiaolan Li

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Human Skeletal Muscle ◽

Muscle Gene Expression ◽

Gene Database ◽

Muscle Gene

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Plasticity of human skeletal muscle: gene expression toin vivofunction

Experimental Physiology ◽

10.1113/expphysiol.2006.036525 ◽

2007 ◽

Vol 92 (5) ◽

pp. 783-797 ◽

Cited By ~ 100

Author(s):

Stephen D. R. Harridge

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Human Skeletal Muscle ◽

Muscle Gene Expression ◽

Muscle Gene

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MuscleAtlasExplorer: a web service for studying gene expression in human skeletal muscle

Database ◽

10.1093/database/baaa111 ◽

2020 ◽

Vol 2020 ◽

Author(s):

Olof Asplund ◽

Johan Rung ◽

Leif Groop ◽

Rashmi Prasad B ◽

Ola Hansson

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Web Application ◽

Human Skeletal Muscle ◽

Sample Selection ◽

Disease Status ◽

Expression Data ◽

Muscle Gene Expression ◽

Phenotype Data ◽

Muscle Gene

Abstract MuscleAtlasExplorer is a freely available web application that allows for the exploration of gene expression data from human skeletal muscle. It draws from an extensive publicly available dataset of 1654 skeletal muscle expression microarray samples. Detailed, manually curated, patient phenotype data, with information such as age, sex, BMI and disease status, are combined with skeletal muscle gene expression to provide insights into gene function in skeletal muscle. It aims to facilitate easy exploration of the data using powerful data visualization functions, while allowing for sample selection, in-depth inspection and further analysis using external tools. Availability: MuscleAtlasExplorer is available at https://mae.crc.med.lu.se/mae2 (username ‘muscle’ and password ‘explorer’ pre-publication).

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Regulation of human skeletal muscle gene expression by aging, resistance exercise, and IL‐1β: identification of candidate mRNAs using a custom real‐time PCR screening method

The FASEB Journal ◽

10.1096/fasebj.21.6.a1309 ◽

2007 ◽

Vol 21 (6) ◽

Author(s):

Richard Dennis ◽

Beata Przybyla ◽

Jonathan Harvey ◽

Patrick Kortebein ◽

William Evans ◽

...

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Resistance Exercise ◽

Real Time Pcr ◽

Human Skeletal Muscle ◽

Screening Method ◽

Pcr Screening ◽

Muscle Gene Expression ◽

Aging Resistance ◽

Muscle Gene

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Exploring the underlying biology of intrinsic cardiorespiratory fitness through integrative analysis of genomic variants and muscle gene expression profiling

Journal of Applied Physiology ◽

10.1152/japplphysiol.00035.2018 ◽

2019 ◽

Vol 126 (5) ◽

pp. 1292-1314

Author(s):

Sujoy Ghosh ◽

Monalisa Hota ◽

Xiaoran Chai ◽

Jencee Kiranya ◽

Palash Ghosh ◽

...

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Cardiorespiratory Fitness ◽

Knockout Mouse ◽

Molecular Mechanisms ◽

Physiological Traits ◽

Muscle Gene Expression ◽

Ranking Scheme ◽

Corroborative Evidence ◽

Muscle Gene

Intrinsic cardiorespiratory fitness (CRF) is defined as the level of CRF in the sedentary state. There are large individual differences in intrinsic CRF among sedentary adults. The physiology of variability in CRF has received much attention, but little is known about the genetic and molecular mechanisms that impact intrinsic CRF. These issues were explored in the present study by interrogating intrinsic CRF-associated DNA sequence variation and skeletal muscle gene expression data from the HERITAGE Family Study through an integrative bioinformatics guided approach. A combined analytic strategy involving genetic association, pathway enrichment, tissue-specific network structure, cis-regulatory genome effects, and expression quantitative trait loci was used to select and rank genes through a variation-adjusted weighted ranking scheme. Prioritized genes were further interrogated for corroborative evidence from knockout mouse phenotypes and relevant physiological traits from the HERITAGE cohort. The mean intrinsic V̇o2max was 33.1 ml O2·kg−1·min−1 (SD = 8.8) for the sample of 493 sedentary adults. Suggestive evidence was found for gene loci related to cardiovascular physiology ( ATE1, CASQ2, NOTO, and SGCG), hematopoiesis ( PICALM, SSB, CA9, and CASQ2), skeletal muscle phenotypes ( SGCG, DMRT2, ADARB1, and CASQ2), and metabolism ( ATE1, PICALM, RAB11FIP5, GBA2, SGCG, PRADC1, ARL6IP5, and CASQ2). Supportive evidence for a role of several of these loci was uncovered via association between DNA variants and muscle gene expression levels with exercise cardiovascular and muscle physiological traits. This initial effort to define the underlying molecular substrates of intrinsic CRF warrants further studies based on appropriate cohorts and study designs, complemented by functional investigations. NEW & NOTEWORTHY Intrinsic cardiorespiratory fitness (CRF) is measured in the sedentary state and is highly variable among sedentary adults. The physiology of variability in intrinsic cardiorespiratory fitness has received much attention, but little is known about the genetic and molecular mechanisms that impact intrinsic CRF. These issues were explored computationally in the present study, with further corroborative evidence obtained from analysis of phenotype data from knockout mouse models and human cardiovascular and skeletal muscle measurements.

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