Obesity-related Differential Gene Expression in the Visceral Adipose Tissue

Baranova, Ancha; Collantes, Rochelle; Gowder, S.; Elariny, Hazem; Schlauch, Karen; Younoszai, Abraham; King, Steve; Randhawa, Manpreet; Pusulury, Sitapati; Alsheddi, Tariq; Ong, Janus P.; Martin, Lisa M.; Chandhoke, Vikas; Younossi, Zobair M.

doi:10.1381/0960892054222876

Cited by 69 publications

(62 citation statements)

References 18 publications

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“…However, the impact of type 2 diabetes has not been examined, and we are the first to report a comparison of gene expression profiles in human subcutaneous and visceral fat of nonobese, obese nondiabetic, and type 2 diabetic subjects. A previous published gene expression profiling on human visceral adipose tissue described the prominent impact of morbid obesity on glycolysis enzymes, oxysterol biosynthesis and signaling, ATP-binding transporters, and solute carriers (37). The absence of a clear impact on electron transport chain genes in that study supports downregulated expression of these genes being directly associated with type 2 diabetes, rather than obesity in general.…”

Section: Discussionmentioning

confidence: 55%

Downregulation of Electron Transport Chain Genes in Visceral Adipose Tissue in Type 2 Diabetes Independent of Obesity and Possibly Involving Tumor Necrosis Factor-α

et al. 2006

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Impaired oxidative phosphorylation is suggested as a factor behind insulin resistance of skeletal muscle in type 2 diabetes. The role of oxidative phosphorylation in adipose tissue was elucidated from results of Affymetrix gene profiling in subcutaneous and visceral adipose tissue of eight nonobese healthy, eight obese healthy, and eight obese type 2 diabetic women. Downregulation of several genes in the electron transport chain was the most prominent finding in visceral fat of type 2 diabetic women independent of obesity, but the gene pattern was distinct from that previously reported in skeletal muscle in type 2 diabetes. A similar but much weaker effect was observed in subcutaneous fat. Tumor necrosis factor-␣ (TNF-␣) is a major factor behind inflammation and insulin resistance in adipose tissue. TNF-␣ treatment decreased mRNA expression of electron transport chain genes and also inhibited fatty acid oxidation when differentiated human preadipocytes were treated with the cytokine for 48 h. Thus, type 2 diabetes is associated with a tissue-and region-specific downregulation of oxidative phosphorylation genes that is independent of obesity and at least in part mediated by TNF-␣, suggesting that impaired oxidative phosphorylation of visceral adipose tissue has pathogenic importance for development of type 2 diabetes. Diabetes 55:1792-1799, 2006

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Section: Discussionmentioning

confidence: 55%

Downregulation of Electron Transport Chain Genes in Visceral Adipose Tissue in Type 2 Diabetes Independent of Obesity and Possibly Involving Tumor Necrosis Factor-α

et al. 2006

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“…Park and Lee (29) reported that OM fat reduction in obese patients induces greater beneficial effects on parameters of the metabolic syndrome than SC fat reduction. Recent studies have shown a differential gene expression in the OM adipose tissue of morbidly obese patients, in particular for genes related to lipid and glucose metabolism, compared with lean individuals (30). We found that AM expression in OM tissue correlates with body composition, systolic blood pressure and some biochemical components involved in the metabolic syndrome.…”

Section: Lean Population (Nz9)mentioning

confidence: 49%

Expression of adrenomedullin in adipose tissue of lean and obese women

et al. 2006

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Objective: Adrenomedullin (AM), a potent vasodilatator and antioxidative peptide, was shown recently to be expressed by adipose tissue. The aim of our study was to investigate the precise localization of AM within human adipose tissue, and to examine AM regulation in obesity. Design: Subcutaneous (SC) and omental (OM) adipose tissues from 9 lean and 13 obese women were profiled for AM expression changes. Preadipocytes from human adipose tissue were isolated and differentiated under defined adipogenic conditions. Methods: AM expression was analyzed by immunohistochemistry, in situ hybridization and quantitative RT-PCR. Results: A strong AM expression was observed in vessel walls, stromal cell clusters and isolated stromal cells, some of them being CD 68 positive, whereas mature adipocytes were not labeled. Calcitonin receptor-like receptor and receptor activity-modifying proteins (RAMP) 2 and RAMP 3 were expressed in vessel walls. In vitro, preadipocytes of early differentiation stages spontaneously secreted AM. No difference in AM localization was found between SC and OM adipose tissue. AM levels in SC tissue did not differ between lean and obese subjects. By contrast, AM levels in OM tissue were significantly higher in obese as compared with lean women. Moreover, we found a positive relationship between OM AM and tumor necrosis factor a mRNA levels and AM-immunoreactive area in OM tissue followed the features of the metabolic syndrome. Conclusion: Stromal cells from human adipose tissue, including macrophages, produce AM. Its synthesis increased in the OM territory during obesity and paralleled the features of the metabolic syndrome. Therefore, AM should be considered as a new member of the adipokine family.

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“…Finally, glucose phosphate isomerase (GPI) is another glycolytic enzyme that is responsible for the conversion of glucose-6-phosphate to fructose-6-phosphate. It has been reported that glycolytic genes, such as GPI and ENO3, are downregulated in the visceral adipose tissue of morbidly obese patients compared with nonobese counterparts (6). Increased GPI expression in subcutaneous fat in response to NBC supplementation is consistent with a myogenic induction of adipose tissue, as GPI is highly expressed in skeletal muscle (9).…”

Section: Niacin-bound Chromium In Obesitymentioning

confidence: 86%

Transcriptome of the subcutaneous adipose tissue in response to oral supplementation of type 2 Lepr^db obese diabetic mice with niacin-bound chromium

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Khanna

et al. 2006

Physiological Genomics

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The effects of oral niacin-bound chromium (NBC) supplementation on the subcutaneous fat tissue of type 2 Lepr db obese diabetic mice were examined using high-density comprehensive mouse genome (45,101 probe sets) expression arrays. The influence of such supplementation on the plasma cardiovascular risk factors of these mice was also investigated. Supplementation of NBC had no significant effect on age-dependent weight gain in the Lepr db obese diabetic mice. However, NBC lowered total cholesterol (TC), TC-to-HDL ratio, LDL cholesterol, and triglyceride levels while increasing HDL cholesterol in the blood plasma. No effect of NBC supplementation was observed on fasting blood glucose levels. Oral glucose tolerance test revealed a significantly improved clearance of blood glucose between 1 and 2 h of glucose challenge in NBC-supplemented mice. Unbiased genome-wide interrogation demonstrated that NBC resulted in the upregulation of muscle-specific gene expression in the fat tissue. Genes encoding proteins involved in glycolysis, muscle contraction, muscle metabolism, and muscle development were specifically upregulated in response to NBC supplementation. Genes in the adipose tissue that were downregulated in response to NBC supplementation included cell death-inducing DNA fragmentation factor (CIDEA) and uncoupling protein-1, which represent key components involved in the thermogenic role of brown adipose tissue and tocopherol transfer protein, the primary carrier of α-tocopherol to adipose tissue. The observation that CIDEA-null mice are resistant to obesity and diabetes suggests that the inhibitory role of NBC on CIDEA expression was favorable. Further studies testing the molecular basis of NBC function and long-term outcomes are warranted.

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Obesity-related Differential Gene Expression in the Visceral Adipose Tissue

Cited by 69 publications

References 18 publications

Downregulation of Electron Transport Chain Genes in Visceral Adipose Tissue in Type 2 Diabetes Independent of Obesity and Possibly Involving Tumor Necrosis Factor-α

Downregulation of Electron Transport Chain Genes in Visceral Adipose Tissue in Type 2 Diabetes Independent of Obesity and Possibly Involving Tumor Necrosis Factor-α

Expression of adrenomedullin in adipose tissue of lean and obese women

Transcriptome of the subcutaneous adipose tissue in response to oral supplementation of type 2 Lepr^db obese diabetic mice with niacin-bound chromium

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Obesity-related Differential Gene Expression in the Visceral Adipose Tissue

Cited by 69 publications

References 18 publications

Downregulation of Electron Transport Chain Genes in Visceral Adipose Tissue in Type 2 Diabetes Independent of Obesity and Possibly Involving Tumor Necrosis Factor-α

Downregulation of Electron Transport Chain Genes in Visceral Adipose Tissue in Type 2 Diabetes Independent of Obesity and Possibly Involving Tumor Necrosis Factor-α

Expression of adrenomedullin in adipose tissue of lean and obese women

Transcriptome of the subcutaneous adipose tissue in response to oral supplementation of type 2 Leprdb obese diabetic mice with niacin-bound chromium

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Transcriptome of the subcutaneous adipose tissue in response to oral supplementation of type 2 Lepr^db obese diabetic mice with niacin-bound chromium