Proteome analysis of human visceral and subcutaneous adipocytes identifies depot-specific heterogeneity at metabolic control points

Abstract

Adipose tissue is a primary regulator of energy balance and metabolism. The distribution of adipose tissue depots is of clinical interest because the accumulation of upper-body subcutaneous (ASAT) and visceral adipose tissue (VAT) is associated with cardiometabolic diseases, whereas lower-body gluteal-femoral adipose tissue (GFAT) appears to be protective. There is heterogeneity in morphology and metabolism of adipocytes obtained from different regions of the body, but detailed knowledge of the constituent proteins in each depot is lacking. Here, we determined the human adipocyte proteome from ASAT, VAT and GFAT using high-resolution SWATH mass spectrometry proteomics. We quantified 4220 proteins in adipocytes, and 2329 proteins were expressed in all three adipose depots. Comparative analysis revealed significant differences between adipocytes from different regions (6 and 8% when comparing VAT vs. ASAT and GFAT, 3% when comparing ASAT vs. GFAT), with marked differences in proteins that regulate metabolic functions. The VAT adipocyte proteome was overrepresented with proteins of glycolysis, lipogenesis, oxidative stress and mitochondrial dysfunction. The GFAT adipocyte proteome predicted activation of PPARa, fatty acid and BCAA oxidation, enhanced TCA cycle flux and oxidative phosphorylation, which was supported by metabolomic data obtained from adipocytes from the same patient donors. Together, this proteomic analysis provides an important resource and novel insights that enhance the understanding of metabolic heterogeneity in the regional adipocytes of humans. 0.0 0.5 1.0 1.5 2.0 2.5 GPD2 GSR PRDX5 CAT SOD2 MAOA OGDH DHODH CYB5R3 CYB5A CYC1 PARK7 HSD17B10 VDAC1 VDAC2 VDAC3

Type 2 Diabetes Mellitus: Pathogenic Features and Experimental Models in Rodents

“…Большое внимание уделяется развитию инновационных технологий в борьбе с распространением СД. Несмотря на огромный прогресс молекулярно-генетических исследований в области СД2 [47][48][49][50][51][52], вопро-сы его профилактики и патогенетического лечения до сих пор не разработаны на должном уровне.…”

“…Much attention is paid to the development of innovative technologies to combat DM. Despite the tremendous progress achieved in molecular genetic research in the field of T2DM [ 47 , 48 , 49 , 50 , 52 , 52 ], measures for its prevention and treatment have not been developed at the proper level yet.…”