6533b823fe1ef96bd127f57d

RESEARCH PRODUCT

Insulin resistance is associated with altered amino acid metabolism and adipose tissue dysfunction in normoglycemic women

Reija AutioPetri WiklundPetri WiklundSirkka Keinänen-kiukaanniemiLingjia KongSulin ChengSulin ChengXiaobo ZhangYifan YangSatu PekkalaMarkku AlenMarkku Alen

subject

0301 basic medicineBlood Glucosemedicine.medical_specialtySubcutaneous FatAdipose tissueGene Expression030209 endocrinology & metabolismInflammationamino acid metabolismBiology3121 Internal medicineta3111Article03 medical and health sciences0302 clinical medicineInsulin resistanceInternal medicineGene expressionmedicineHumansAmino AcidsPhosphorylationMuscle Skeletalchemistry.chemical_classificationInflammationadiposityMultidisciplinaryAnthropometryCatabolismSisätaudit - Internal medicineSkeletal muscleNaisten- ja lastentaudit - Gynaecology and paediatricsmedicine.diseaseinsuliiniresistenssi113 Computer and information sciencesAmino acidadipose tissue3141 Health care science030104 developmental biologyEndocrinologymedicine.anatomical_structurechemistryAdipose TissueBody CompositionFemaleSignal transductionmedicine.symptomInsulin ResistanceSignal Transduction

description

AbstractInsulin 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.

10.1038/srep24540http://europepmc.org/articles/PMC4832240