Defining the Human Adipose Tissue Proteome To Reveal Metabolic Alterations in Obesity
Journal article, 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



white adipose tissue



Adil Mardinoglu

Chalmers, Chemical and Biological Engineering, Life Sciences

C. Kampf

Uppsala University

A. Asplund

Uppsala University

L. Fagerberg

Royal Institute of Technology (KTH)

B. M. Hallstrom

Royal Institute of Technology (KTH)

K. Edlund

Uppsala University

M. Bluher

Leipzig University

F. Ponten

Uppsala University

M. Uhlen

Royal Institute of Technology (KTH)

Jens B Nielsen

Chalmers, Chemical and Biological Engineering, Life Sciences

Journal of Proteome Research

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

Vol. 13 11 5106-5119

Metagenomics in Cardiometabolic Diseases (METACARDIS)

European Commission (EC) (EC/FP7/305312), 2012-11-01 -- 2017-10-31.

Subject Categories

Biochemistry and Molecular Biology


C3SE (Chalmers Centre for Computational Science and Engineering)

Areas of Advance

Life Science Engineering (2010-2018)



More information

Latest update

3/5/2018 8