TY - JOUR

T1 - Subcutaneous adipose tissue and systemic inflammation are associated with peripheral but not hepatic insulin resistance in humans

AU - van der Kolk, Birgitta W

AU - Kalafati, Marianthi

AU - Adriaens, Michiel

AU - van Greevenbroek, Marleen M J

AU - Vogelzangs, Nicole

AU - Saris, Wim H M

AU - Astrup, Arne

AU - Valsesia, Armand

AU - Langin, Dominique

AU - van der Kallen, Carla J H

AU - Eussen, Simone J P M

AU - Schalkwijk, Casper G

AU - Stehouwer, Coen D A

AU - Goossens, Gijs H

AU - Arts, Ilja C W

AU - Jocken, Johan W E

AU - Evelo, Chris T

AU - Blaak, Ellen E

N1 - © 2019 by the American Diabetes Association.

PY - 2019

Y1 - 2019

N2 - Obesity-related insulin resistance (IR) may develop in multiple organs, representing different etiologies towards cardiometabolic diseases. We identified abdominal subcutaneous adipose tissue (ScAT) transcriptome profiles in relation to liver or muscle IR by means of RNA sequencing in overweight/obese participants of the DiOGenes cohort (n=368). Tissue-specific IR phenotypes were derived from a 5-point oral glucose tolerance test. Hepatic and muscle IR were characterized by distinct abdominal ScAT transcriptome profiles. Genes related to extracellular remodeling were upregulated in individuals with primarily hepatic IR, whilst genes related to inflammation were upregulated in individuals with primarily muscle IR. In line with this, in two independent cohorts, CODAM (n=325) and the Maastricht Study (n=685), an increased systemic low-grade inflammation profile was specifically related to muscle IR, but not to liver IR. We propose that increased ScAT inflammatory gene expression may translate into an increased systemic inflammatory profile, linking ScAT inflammation to the muscle IR phenotype. These distinct IR phenotypes may provide leads for more personalized prevention of cardiometabolic diseases. DiOGenes was registered at clinicaltrials.gov as NCT00390637.

AB - Obesity-related insulin resistance (IR) may develop in multiple organs, representing different etiologies towards cardiometabolic diseases. We identified abdominal subcutaneous adipose tissue (ScAT) transcriptome profiles in relation to liver or muscle IR by means of RNA sequencing in overweight/obese participants of the DiOGenes cohort (n=368). Tissue-specific IR phenotypes were derived from a 5-point oral glucose tolerance test. Hepatic and muscle IR were characterized by distinct abdominal ScAT transcriptome profiles. Genes related to extracellular remodeling were upregulated in individuals with primarily hepatic IR, whilst genes related to inflammation were upregulated in individuals with primarily muscle IR. In line with this, in two independent cohorts, CODAM (n=325) and the Maastricht Study (n=685), an increased systemic low-grade inflammation profile was specifically related to muscle IR, but not to liver IR. We propose that increased ScAT inflammatory gene expression may translate into an increased systemic inflammatory profile, linking ScAT inflammation to the muscle IR phenotype. These distinct IR phenotypes may provide leads for more personalized prevention of cardiometabolic diseases. DiOGenes was registered at clinicaltrials.gov as NCT00390637.

U2 - 10.2337/db19-0560

DO - 10.2337/db19-0560

M3 - Journal article

C2 - 31492661

VL - 68

SP - 2247

EP - 2258

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 12

ER -