Looking for Protein Changes in Type 2 Diabetes and Obesity

It isn’t just problematic for swimsuit season: visceral adipose tissue, sometimes called belly fat, is found deep in the stomach and abdominal region, wrapping around the intestines, omentum and peritoneal cavity. Visceral adipose tissue is a major endocrine organ. It secretes hormones and functions to store energy. Large accumulations of visceral adipose tissue, for example in clinically obese individuals, mean an increase in these hormones. This, in turn, leads to increased risks of type 2 diabetes (T2DM) as well as inflammatory diseases. Knowing that obesity is on the rise, Gómez-Serrano et al. looked for T2DM markers in visceral adipose tissue with the aim of enhancing diagnostics and gaining new insights into aging and obesity.¹

The researchers adopted a high-throughput proteomics approach encompassing peptide labeling with isobaric tags for relative and absolute quantitation (iTRAQ). They also used liquid chromatography by way of an EASY-nLC 1000 nano-HPLC apparatus and mass spectrometry using a Q Exactive Hybrid Quadrupole-Orbitrap mass spectrometer (both Thermo Scientific). The visceral adipose tissue for study came from a subgroup of 16 obese patients (body mass index ≥ 40 kg/m²). The investigators selected these patients out of 50 initial subjects who underwent bariatric surgery. The subjects consisted of two main groups: patients with T2DM (diabetic obese, n = 8) and patients without T2DM or other obesity-associated comorbidity (non-diabetic obese, n = 8). They split each of these groups into two subgroups based on gender (diabetic women, n = 4; diabetic men, n = 4) and age (non-diabetic women over 45 years, n = 4; non-diabetic women under 35 years, n = 4).

As a result, the researchers identified 14,118 unique peptides corresponding to 2,525 unique proteins. Looking at the biological relevance, the authors reported that protein functions are involved in the generation of precursor metabolites and energy, glucose and fatty acid metabolic processes, and oxidative stress responses.

They found a total of 255 differentially expressed proteins, comparing older (mean age 50 years) and younger women (mean age 32 years). They also saw 203 proteins with expression changes between diabetic and non-diabetic women. Comparing men and women, they found changes in 246 proteins. Interestingly, the T2DM and gender comparisons showed the greatest overlap of differentially expressed proteins (33%), suggesting a high impact of gender on the diabetic phenotype. In women, they saw overexpression of extracellular region and immune response–related terms, and in men, the upregulated proteins mainly related to oxidation reduction and glutathione transferase activity.

In diabetic and non-diabetic patients, the researchers linked upregulated proteins to calcium binding, immune response and inflammation. They linked downregulated proteins to mitochondrial structure and function, such as the generation of precursor metabolites and energy, ATP synthesis and pyruvate metabolism.

In older compared to younger patients, the team identified downregulated proteins linked to protein synthesis, chromatin remodeling, mRNA processing, mRNA binding, nucleosomal and ribosomal proteins, translation and chromosome organization. The age-based comparison also unveiled the upregulation of proteins and categories related to extracellular matrix organization, the largest cluster of overrepresented categories associated with aging.

Taken together, these findings could serve as a framework for future research in translational medicine directed at improving the quality of life of obese patients.

Reference
1. Gómez-Serrano, M., et al. (2016) “Proteome-wide alterations on adipose tissue from obese patients as age-, diabetes- and gender-specific hallmarks,” Scientific Reports, 6(25756), doi: 10.1038/srep25756.