Dataset Information

Cathepsin gene expression in abdominal subcutaneous adipose tissue of obese/overweight humans.

ABSTRACT: Cathepsin L1 (CTSL1) and B (CTSB) are lysosomal proteases, of which the expression and activity are impaired in adipose tissue (AT) of obese rodents, indicating AT lysosomal dysfunction. Here we assess the relation between abdominal subcutaneous AT (SCAT) CTSL1 and CTSB gene expression (qRT-PCR), body composition and tissue-specific insulin resistance in 77 overweight/obese (BMI: 225.6-38.6 kg/m²) well phenotyped men and women (61 M/16 F). A two-step hyperinsulinemic-euglycemic clamp was performed to assess AT, hepatic and skeletal muscle insulin sensitivity. Our data show that reduced CTSB expression is associated with markers of insulin resistance (standardized β = -0.561, p < 0.001), independent of adiposity, while CTSL1 expression is only associated with markers of body composition. Our data suggest the presence of lysosomal dysfunction in SCAT of obese humans with an impaired glucose homoeostasis. However, this needs to be investigated in more detail in future mechanistic studies.

SUBMITTER: Xu Q

PROVIDER: S-EPMC7469552 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cathepsin gene expression in abdominal subcutaneous adipose tissue of obese/overweight humans.

Xu Qing Q Mariman Edwin C M ECM Goossens Gijs H GH Blaak Ellen E EE Jocken Johan W E JWE

Adipocyte 20200101 1

Cathepsin L1 (CTSL1) and B (CTSB) are lysosomal proteases, of which the expression and activity are impaired in adipose tissue (AT) of obese rodents, indicating AT lysosomal dysfunction. Here we assess the relation between abdominal subcutaneous AT (SCAT) CTSL1 and CTSB <i>gene</i> expression (qRT-PCR), body composition and tissue-specific insulin resistance in 77 overweight/obese (BMI: 225.6-38.6 kg/m<sup>2</sup>) well phenotyped men and women (61 M/16 F). A two-step hyperinsulinemic-euglycemic ...[more]

PMID: 32486882

Similar Datasets

Project description:BackgroundAccumulation of visceral adipose tissue (VAT) is clearly associated with an increased risk of obesity-related diseases and all-cause mortality, whereas gluteal subcutaneous fat accumulation (g-SAT) is associated with a lower risk. The relative contribution, in term of cardiovascular risk, of abdominal subcutaneous adipose tissue (a-SAT) is still controversial with studies showing both a detrimental effect and a protective role. Animal and in vitro studies demonstrated that adipocytes from visceral and subcutaneous depots have distinct morphological, metabolic and functional characteristics. These regional differences have a key role in the pathogenesis of obesity-related diseases. There is recent evidence that differentiation between upper-body and lower-body adipose tissues might be under control of site-specific sets of developmental genes, such as Homebox (HOX) genes, a group of related genes that control the body plan of an embryo along the anterior-posterior axis. However, the possible heterogeneity between different subcutaneous regions has not been extensively investigated. Here we studied global mRNA expression in g-SAT and a-SAT with a microarray approach. RNA was isolated from g-SAT and a-SAT biopsy, from eight healthy subjects, and hybridized on RNA microarray chips in order to detect regional differences in gene expression.ResultsA total of 131 genes are significantly and differently (>1.5 fold change, p < 0.05) expressed in a-SAT and g-SAT. Expression profiling reveals significant differences in expression of several HOX genes. Interestingly, two molecular signature of visceral adipocyte lineage, homebox genes HOXA5 and NR2F1, are up-regulated in a-SAT versus g-SAT by a 2.5 fold change.ConclusionsOur study shows that g-SAT and a-SAT have distinct expression profiles. The finding of a different expression of HOX genes, fundamental during the embryo development, suggests an early regional differentiation of subcutaneous adipose depots. Moreover, the higher expression of HOXA5 and NR2F1, two molecular signatures of visceral adipocytes, in a-SAT suggests that this subcutaneous adipose depot could be more similar to VAT than g-SAT. Our data suggest that we should look at SAT as composed of distinct depots with possibly different impact in obesity associated metabolic complications.

Dataset Information

Cathepsin gene expression in abdominal subcutaneous adipose tissue of obese/overweight humans.

Publications

Cathepsin gene expression in abdominal subcutaneous adipose tissue of obese/overweight humans.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets