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A protein profile of visceral adipose tissues linked to early pathogenesis of type 2 diabetes mellitus.

ABSTRACT: Adipose tissue is increasingly recognized as an endocrine organ playing important pathophysiological roles in metabolic abnormalities, such as obesity, cardiovascular disease, and type 2 diabetes mellitus (T2DM). In particular, visceral adipose tissue (VAT), as opposed to subcutaneous adipose tissue, is closely linked to the pathogenesis of insulin resistance and T2DM. Despite the importance of VAT, its molecular signatures related to the pathogenesis of T2DM have not been systematically explored. Here, we present comprehensive proteomic analysis of VATs in drug-naïve early T2DM patients and subjects with normal glucose tolerance. A total of 4,707 proteins were identified in LC-MS/MS experiments. Among them, 444 increased in abundance in T2DM and 328 decreased. They are involved in T2DM-related processes including inflammatory responses, peroxisome proliferator-activated receptor signaling, oxidative phosphorylation, fatty acid oxidation, and glucose metabolism. Of these proteins, we selected 11 VAT proteins that can represent alteration in early T2DM patients. Among them, up-regulation of FABP4, C1QA, S100A8, and SORBS1 and down-regulation of ACADL and PLIN4 were confirmed in VAT samples of independent early T2DM patients using Western blot. In summary, our profiling provided a comprehensive basis for understanding the link of a protein profile of VAT to early pathogenesis of T2DM.

SUBMITTER: Kim SJ

PROVIDER: S-EPMC3945910 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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A protein profile of visceral adipose tissues linked to early pathogenesis of type 2 diabetes mellitus.

Kim Su-Jin SJ Chae Sehyun S Kim Hokeun H Mun Dong-Gi DG Back Seunghoon S Choi Hye Yeon HY Park Kyong Soo KS Hwang Daehee D Choi Sung Hee SH Lee Sang-Won SW

Molecular & cellular proteomics : MCP 20140108 3

Adipose tissue is increasingly recognized as an endocrine organ playing important pathophysiological roles in metabolic abnormalities, such as obesity, cardiovascular disease, and type 2 diabetes mellitus (T2DM). In particular, visceral adipose tissue (VAT), as opposed to subcutaneous adipose tissue, is closely linked to the pathogenesis of insulin resistance and T2DM. Despite the importance of VAT, its molecular signatures related to the pathogenesis of T2DM have not been systematically explore ...[more]

PMID: 24403596

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Project description:BACKGROUND:Lipid intermediates produced during triacylglycerols (TAGs) synthesis and lipolysis in adipocytes interfere with the intracellular insulin signaling pathway and development of insulin resistance. This study aims to compare TAG species and their fatty acid composition in adipose tissues from insulin sensitive (IS), insulin resistant (IR) and type 2 diabetes mellitus (T2DM) obese individuals. METHODS:Human subcutaneous and omental adipose tissue biopsies were obtained from 64 clinically characterized obese individuals during weight reduction surgery. TAGs were extracted from the adipose tissues using the Bligh and Dyer method, then were subjected to non-aqueous reverse phase ultra-high performance liquid chromatography and full scan mass spectrometry acquisition and data dependent MS/MS on LTQ dual cell linear ion trap. TAGs and their fatty acid contents were identified and compared between IS, IR and T2DM individuals and their levels were correlated with metabolic traits of participants and the adipogenic potential of preadipocyte cultures established from their adipose tissues. RESULTS:Data revealed 76 unique TAG species in adipose tissues identified based on their exact mass. Analysis of TAG levels revealed a number of TAGs that were significantly altered with disease progression including C46:4, C48:5, C48:4, C38:1, C50:3, C40:2, C56:3, C56:4, C56:7 and C58:7. Enrichment analysis revealed C12:0 fatty acid to be associated with TAGs least abundant in T2DM whereas C18:3 was found in both depleted and enriched TAGs in T2DM. Significant correlations of various adipose tissue-derived TAG species and metabolic traits were observed, including age and body mass index, systemic total cholesterol, TAGs, and interleukin-6 in addition to adipogenic potential of preadipocytes derived from the same adipose tissues. CONCLUSION:Pilot data suggest that adipose tissues from obese IR and T2DM individuals exhibit TAG-specific signatures that may contribute to their increased risk compared to their IS counterparts. Future experiments are warranted to investigate the functional relevance of these specific lipidomic profiles.

Project description:Increasing evidence has shown that insulin resistance in omental visceral adipose tissue (OVAT) is a characteristic of gestational diabetes mellitus (GDM). The present study aimed to identify differentially expressed genes (DEGs) and their associated functions and pathways involved in the pathogenesis of GDM by comparing the expression profiles of OVATs obtained from pregnant Chinese women with and without GDM during caesarian section. A total of 935 DEGs were identified, including 450 downregulated and 485 upregulated genes. In the gene ontology category cellular components, the DEGs were predominantly associated with functions of the extracellular region, while receptor binding was predominant in the molecular function category and biological process terms included antigen processing and presentation, extracellular matrix organization, positive regulation of cell-substrate adhesion, response to nutrients and response to dietary excess. Functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed and a functional interaction network was constructed. Functions of downregulated genes included antigen processing and presentation as well as cell adhesion molecules, while those of upregulated genes included transforming growth factor (TGF)-β-signaling, focal adhesion, phosphoinositide-3 kinase-Akt-signaling, P53 signaling, extracellular matrix-receptor interaction and regulation of actin cytoskeleton pathway. The five main pathways associated with GDM were antigen processing and presentation, cell adhesion molecules, Type 1 diabetes mellitus, natural killer cell-mediated cytotoxicity and TGF-β signaling. These pathways were included in the KEGG pathway categories of 'signaling molecules and interaction', 'immune system' and 'inflammatory response', suggesting that these processes are involved in GDM. The results of the present study enhanced the present understanding of the mechanisms associated with insulin resistance in OVATs of GDM.

Project description:BACKGROUND Human visceral adipose tissue (VAT), now identified as an endocrine organ, plays a significant role in impaired fasting glucose and diabetes through the deregulated metabolism and adipogenesis of visceral adipocytes in obesity. Our study focuses on exploring the link between inflammation, oxidative stress, and glucose metabolism-associated genes with corresponding miRNAs in human visceral adipocytes and VAT from individuals with glucose metabolism disorders. MATERIAL AND METHODS We examined the expression of ATM, NFKB1, SOD2, INSR, and TIGAR, along with their related miRNAs using PCR, in two contexts:1 - During the three-stage visceral adipogenesis under normal glucose levels (5.5 millimoles), intermittent, and chronic hyperglycemia (30 millimoles).2 - In visceral adipose tissue from subjects (34 F, 18 M) with normal glucose metabolism, impaired fasting glucose, and type 2 diabetes mellitus. RESULTS Both chronic and intermittent hyperglycemia similarly influenced ATM, NFKB1, TIGAR, SOD2, INSR gene expression in visceral adipocytes, with corresponding changes in a few tested miRNAs (eg, let-7g-5p, miR-145-5p, miR-21-5p). Anthropometric and biochemical parameters led us to focus on female subjects. Our results showed transactivation of NFKB1, TIGAR, miR-10b-5p, miR-132-3p, miR-20a-5p, miR-21-5p, and miR-26a-5p exclusively in type 2 diabetes mellitus. Upregulated molecules (excluding miR-10b-5p and miR-20a-5p) positively correlated with glucose metabolism markers. CONCLUSIONS The genes studied may undergo miRNA interferences and hyperglycemic memory in visceral adipocytes under hyperglycemic conditions. VAT from women with type 2 diabetes mellitus, but not with impaired fasting glucose, showed transactivated miRNAs and a molecular dysregulation of TIGAR and NFKB1, possibly enhancing inflammation, oxidative stress, and disrupted glucose metabolism. These findings highlight the epigenetic and molecular disturbances in VAT related to glucose metabolism abnormalities. However, additional research is necessary to further understand their biological significance.

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A protein profile of visceral adipose tissues linked to early pathogenesis of type 2 diabetes mellitus.

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A protein profile of visceral adipose tissues linked to early pathogenesis of type 2 diabetes mellitus.

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