title: Insulin resistance is associated with altered amino acid metabolism and adipose tissue dysfunction in normoglycemic women.
abstract: Insulin resistance is associated adiposity, but the mechanisms are not fully understood. In this study, we aimed to identify early metabolic alterations associated with insulin resistance in normoglycemic women with varying degree of adiposity. One-hundred and ten young and middle-aged women were divided into low and high IR groups based on their median HOMA-IR (0.9 ± 0.4 vs. 2.8 ± 1.2). Body composition was assessed using DXA, skeletal muscle and liver fat by proton magnetic resonance spectroscopy, serum metabolites by nuclear magnetic resonance spectroscopy and adipose tissue and skeletal muscle gene expression by microarrays. High HOMA-IR subjects had higher serum branched-chain amino acid concentrations (BCAA) (p < 0.05 for both). Gene expression analysis of subcutaneous adipose tissue revealed significant down-regulation of genes related to BCAA catabolism and mitochondrial energy metabolism and up-regulation of several inflammation-related pathways in high HOMA-IR subjects (p < 0.05 for all), but no differentially expressed genes in skeletal muscle were found. In conclusion, in normoglycemic women insulin resistance was associated with increased serum BCAA concentrations, down-regulation of mitochondrial energy metabolism and increased expression of inflammation-related genes in the adipose tissue.
authors.affiliation: Shanghai Jiao Tong University, Shanghai, China.|Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland.
authors.forename: Petri
authors.initials: P
authors.lastname: Wiklund
authors.affiliation: Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland.
authors.forename: Satu
authors.initials: S
authors.lastname: Pekkala
authors.affiliation: School of Health Sciences, University of Tampere, Tampere, Finland.
authors.forename: Reija
authors.initials: R
authors.lastname: Autio
authors.affiliation: Department of Signal Processing, Tampere University of Technology, Tampere, Finland.
authors.forename: Lingjia
authors.initials: L
authors.lastname: Kong
authors.affiliation: Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Center for Life Course Health Research, University of Oulu, Oulu, Finland.
authors.forename: Sirkka
authors.initials: S
authors.lastname: Keinänen-Kiukaanniemi
authors.affiliation: Center for Life Course Health Research, University of Oulu, Oulu, Finland.|Department of Medical Rehabilitation, Oulu University Hospital, Oulu, Finland.
authors.forename: Markku
authors.initials: M
authors.lastname: Alen
authors.affiliation: Shanghai Jiao Tong University, Shanghai, China.|Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland.
authors.forename: Sulin
authors.initials: S
authors.lastname: Cheng
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism*; D000886:Anthropometry; D001786:Blood Glucose; D001823:Body Composition; D005260:Female; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance; D018482:Muscle, Skeletal / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D050151:Subcutaneous Fat / Q000378:metabolism
chemical_list: D000596:Amino Acids; D001786:Blood Glucose