Depot-related gene expression in human subcutaneous and omental adipocytes.

Montague, Carl; Prins, J. B.; Sanders, Laura; Zhang, Junlong; Sewter, Ciaran; Digby, J; Byrne, Christopher D.; O’Rahilly, Stephen

doi:10.2337/diabetes.47.9.1384

Cited by 314 publications

(280 citation statements)

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“…Montague and colleagues show that expression of Tnfa and other genes varied among adipose tissue depots in humans. (51) Expression levels of both Adipoq, an adipokine that plays an important role in modulating insulin action and inhibiting gluconeogenesis, (52) and Slc2A4/Glut4 were increased in leptintreated mice, which is consistent with the improved insulin sensitivity of the mice treated with leptin in both this study and our previous one. As expected, expression of Lep (leptin) was decreased after both SC and ICV leptin treatments.…”

Section: Discussionsupporting

confidence: 91%

Central (ICV) leptin injection increases bone formation, bone mineral density, muscle mass, serum IGF-1, and the expression of osteogenic genes in leptin-deficient ob/ob mice

Bartell

Rayalam

Ambati

et al. 2011

Journal of Bone and Mineral Research

138

117

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Both central and peripheral leptin administrations reduce body weight, food intake, and adiposity in ob/ob mice. In this study we compared effects of intracerebroventricular (ICV) and subcutaneous (SC) administration of leptin on bone metabolism in the appendicular and axial skeleton and adipose tissue gene expression and determined the effects of ICV leptin on bone marrow gene expression in ob/ob mice. In experiment 1, leptin (1.5 or 0.38 mg/d) or control was continuously injected ICV for 12 days. Gene expression analysis of femoral bone marrow stromal cells showed that expression of genes associated with osteogenesis was increased after ICV injection, whereas those associated with osteoclastogenesis, adipogenesis, and adipocyte lipid storage were decreased. In experiment 2, leptin was injected continuously ICV (0.0 or 1.5 mg/d) or SC (0.0 or 10 mg/d) for 12 days. In both experiments, regardless of mode of administration, leptin decreased body weight, food intake, and body fat and increased muscle mass, bone mineral density, bone mineral content, bone area, marrow adipocyte number, and mineral apposition rate. Serum insulin was decreased, whereas serum osteocalcin, insulin-like growth factor 1, osteoprotegerin, pyridinoline, and receptor activator of nuclear factor kB ligand concentrations were increased. In experiment 2, expression of genes in adipose tissue associated with apoptosis, lipid mobilization, insulin sensitivity, and thermogenesis was increased, whereas expression of genes associated with cell differentiation and maturation was decreased regardless of mode of administration. Thus ICV injection of leptin promotes expression of pro-osteogenic factors in bone marrow, leading to enhanced bone formation in ob/ob mice. ß

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Section: Discussionsupporting

confidence: 91%

Central (ICV) leptin injection increases bone formation, bone mineral density, muscle mass, serum IGF-1, and the expression of osteogenic genes in leptin-deficient ob/ob mice

Bartell

Rayalam

Ambati

et al. 2011

Journal of Bone and Mineral Research

138

117

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“…Despite a very wide age range in our study material, we found no significant correlation between age and PPRE activity in the subcutaneous or intra-abdominal fat cells. It has earlier been shown that BMI and mRNA for PPARG are inversely related in subcutaneous fat cells [21]. However, we found no correlation between PPRE activity and BMI in either subcutaneous or intra-abdominal fat cells.…”

Section: Discussioncontrasting

confidence: 81%

“…This was confirmed by quantification of PPARG receptor in the two tissues, showing 55% higher levels of the receptor in omental fat cells. Furthermore, Montague et al have shown that the levels of mRNA for PPARG are not different in subcutaneous and omental human fat cells [21].…”

Section: Discussionmentioning

confidence: 99%

Peroxisome proliferator activated receptor gamma activity is low in mature primary human visceral adipocytes

et al. 2006

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Aims/hypothesis The amount of visceral fat mass strongly relates to insulin resistance in humans. The transcription factor peroxisome proliferator activated receptor gamma (PPARG) is abundant in adipocytes and regulates genes of importance for insulin sensitivity. Our objective was to study PPARG activity in human visceral and subcutaneous adipocytes and to compare this with the most common model for human disease, the mouse. Materials and methods We transfected primary human adipocytes with a plasmid encoding firefly luciferase controlled by PPARG response element (PPRE) from the acyl-CoA-oxidase gene and measured PPRE activity by emission of light.Results We found that PPRE activity was 6.6-fold higher (median) in adipocytes from subcutaneous than from omental fat from the same subjects (n=23). The activity was also 6.2-fold higher in subcutaneous than in intraabdominal fat cells when we used a PPARG ligand-binding domain-GAL4 fusion protein as reporter, demonstrating that the difference in PPRE activity was due to different levels of activity of the PPARG receptor in the two fat depots. Stimulation with 5 μmol/l rosiglitazone did not induce a PPRE activity in visceral adipocytes that was as high as basal levels in subcutaneous adipocytes. Interestingly, in mice of two different strains the PPRE activity was similar in visceral and subcutaneous fat cells. Conclusions/interpretation We found considerably lower PPARG activity in visceral than in subcutaneous primary human adipocytes. Further studies of the molecular mechanisms behind this difference could lead to development of drugs that target the adverse effects of visceral obesity.

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“…Differences in gene expression of adipocyte-secreted molecules suggest that there are intrinsic fat depot-specific differences in the endocrine function of adipose tissue. Differentially expressed adipokines include leptin (Montague et al, 1998), plasminogen activator inhibitor-1 (Alessi et al, 1997), IL-6 (Fried et al, 1998) and visfatin (Fukuhara et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Orosomucoid Serum Concentrations and Fat Depot-Specific mRNA and Protein Expression in Humans

Alfadda

Fatma

Chishti

et al. 2012

Molecules and Cells

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Obesity is associated with chronic low-grade inflammation, which contributes to systemic metabolic irregularities and obesity-linked metabolic disorders. Orosomucoid (ORM), an acute phase reactant protein, was shown to be produced in response to metabolic and inflammatory signals in the adipose tissue of obese mice, which protects them from severe inflammation and subsequent metabolic dysfunction. In this study, we examined whether there are sitespecific differences between visceral and subcutaneous adipose tissue (VAT and SAT, respectively) ORM gene and protein expression from individuals with a wide range of obesity and the relationship between expressed and circulating ORM levels and measures of adiposity, insulin resistance, and pro-and anti-inflammatory markers and adipokines. The level of circulating ORM correlated positively with BMI, body fat mass, and serum leptin. It also correlated with fasting insulin, HOMA-IR values and C-reactive protein in men. There were no site-specific differences in ORM mRNA and protein expression between VAT and SAT, nor did we find a relationship between circulating ORM levels and its mRNA expression in either fat depot. We found that ORM mRNA expression correlated with mRNA expression of TNF-α, IL-6, and adiponectin in VAT, and with TNF-α and adiponectin in SAT. These observations are the first description linking adipose tissue ORM and pro-and anti-inflammatory molecules in humans. The close links of ORM and measures of adiposity, insulin resistance, and adipose tissue inflammation in humans reinforce previous experimental data and warrant further studies to explore a possible role of ORM in the pathogenesis of obesity-associated metabolic derangements.

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Depot-related gene expression in human subcutaneous and omental adipocytes.

Cited by 314 publications

References 0 publications

Central (ICV) leptin injection increases bone formation, bone mineral density, muscle mass, serum IGF-1, and the expression of osteogenic genes in leptin-deficient ob/ob mice

Central (ICV) leptin injection increases bone formation, bone mineral density, muscle mass, serum IGF-1, and the expression of osteogenic genes in leptin-deficient ob/ob mice

Peroxisome proliferator activated receptor gamma activity is low in mature primary human visceral adipocytes

Orosomucoid Serum Concentrations and Fat Depot-Specific mRNA and Protein Expression in Humans

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