Defining the Human Adipose Tissue Proteome To Reveal Metabolic Alterations in Obesity
Artikel i vetenskaplig tidskrift, 2014

White adipose tissue (WAT) has a major role in the progression of obesity. Here, we combined data from RNA-Seq and antibody-based immunohistochemistry to describe the normal physiology of human WAT obtained from three female subjects and explored WAT-specific genes by comparing WAT to 26 other major human tissues. Using the protein evidence in WAT, we validated the content of a genome-scale metabolic model for adipocytes. We employed this high-quality model for the analysis of subcutaneous adipose tissue (SAT) gene expression data obtained from subjects included in the Swedish Obese Subjects Sib Pair study to reveal molecular differences between lean and obese individuals. We integrated SAT gene expression and plasma metabolomics data, investigated the contribution of the metabolic differences in the mitochondria of SAT to the occurrence of obesity, and eventually identified cytosolic branched-chain amino acid (BCAA) transaminase 1 as a potential target that can be used for drug development. We observed decreased glutaminolysis and alterations in the BCAAs metabolism in SAT of obese subjects compared to lean subjects. We also provided mechanistic explanations for the changes in the plasma level of BCAAs, glutamate, pyruvate, and alpha-ketoglutarate in obese subjects. Finally, we validated a subset of our model-based predictions in 20 SAT samples obtained from 10 lean and 10 obese male and female subjects.

genome-scale metabolic modeling

proteome

transcriptome

white adipose tissue

adipocytes

Författare

Adil Mardinoglu

Chalmers, Kemi- och bioteknik, Livsvetenskaper, Systembiologi

C. Kampf

Uppsala universitet

A. Asplund

Uppsala universitet

L. Fagerberg

Kungliga Tekniska Högskolan (KTH)

B. M. Hallstrom

Kungliga Tekniska Högskolan (KTH)

K. Edlund

Uppsala universitet

M. Bluher

Universität Leipzig

F. Ponten

Uppsala universitet

M. Uhlen

Kungliga Tekniska Högskolan (KTH)

Jens B Nielsen

Chalmers, Kemi- och bioteknik, Livsvetenskaper, Systembiologi

Journal of Proteome Research

1535-3893 (ISSN) 1535-3907 (eISSN)

Vol. 13 11 5106-5119

Metagenomics in Cardiometabolic Diseases (METACARDIS)

Europeiska kommissionen (FP7), 2012-11-01 -- 2017-10-31.

Ämneskategorier

Biokemi och molekylärbiologi

Infrastruktur

C3SE (Chalmers Centre for Computational Science and Engineering)

Styrkeområden

Livsvetenskaper och teknik

DOI

10.1021/pr500586e

Mer information

Senast uppdaterat

2018-03-05