Hunting for human obesity genes? Look in the adipose tissue!

Arner, Peter

doi:10.1038/sj.ijo.0801507

Cited by 31 publications

(25 citation statements)

References 21 publications

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“…3 Up to now, primarily genes with an established function in adipocytes in experimental models have been analysed for allelic association with obesity. Developments in genomics, in particular expression profiling with cDNA or in situ synthesized oligonucleotide microarrays allowing parallel quantification of thousands of different transcripts, have provided scientists with a number of new candidate genes whose expression in adipose tissue is regulated by obesity or weight change.…”

Section: Modern Approaches To Discover Adipose Tissue Genes Contributmentioning

confidence: 99%

Obesity and polymorphisms in genes regulating human adipose tissue

Dahlman

Arner

2007

Int J Obes

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Obesity is the result of an imbalance between food intake and energy expenditure resulting in the storing of energy as fat. Adipose tissue contains the largest store of energy in the body and plays important roles in regulating energy partitioning. Developments in genomics, in particular microarray-based expression profiling, have provided scientists with a number of new candidate genes whose expression in adipose tissue is regulated by obesity. Integrating expression profiles with genome-wide linkage and/or association analyses is a promising strategy to identify new genes underlying susceptibility to obesity. This article provides a comprehensive review of adipose-tissue-expressed genes implicated in predisposition to human obesity. The authors consider the following genes of particular interest: peroxisome proliferator-activated receptor gamma and, potentially, INSIG2 acting in adipogenesis; the adrenoreceptors beta 2 and 3, as well as hormone-sensitive lipase acting on lipolysis; uncoupling protein 2 acting in mitochondria energy expenditure; and among secreted molecules the cytokine tumor necrosis factor alpha and the hormone leptin. With the rapid development in genome research, we predict that additional alleles in genes regulating adipose tissue function will be established as risk factors for common obesity in the coming years. This has important implications for the prevention of obesity and may also offer new therapeutic targets.

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Section: Modern Approaches To Discover Adipose Tissue Genes Contributmentioning

confidence: 99%

Obesity and polymorphisms in genes regulating human adipose tissue

Dahlman

Arner

2007

Int J Obes

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“…The role of adipose tissue in the aetiology of obesity [7], as well as its pathophysiological consequences [8], is increasingly being recognised. A few studies in rodents and humans have used microarray gene expression profiling of whole adipose tissue to investigate its role in obesity [9,10].…”

Section: Introductionmentioning

confidence: 99%

Microarray profiling of isolated abdominal subcutaneous adipocytes from obese vs non-obese Pima Indians: increased expression of inflammation-related genes

et al. 2005

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Aims/hypothesis: Obesity increases the risk of developing major diseases such as diabetes and cardiovascular disease. Adipose tissue, particularly adipocytes, may play a major role in the development of obesity and its comorbidities. The aim of this study was to characterise, in adipocytes from obese people, the most differentially expressed genes that might be relevant to the development of obesity. Methods: We carried out microarray gene profiling of isolated abdominal subcutaneous adipocytes from 20 non-obese (BMI 25±3 kg/m 2 ) and 19 obese (BMI 55± 8 kg/m 2 ) non-diabetic Pima Indians using Affymetrix HG-U95 GeneChip arrays. After data analyses, we measured the transcript levels of selected genes based on their biological functions and chromosomal positions using quantitative real-time PCR. Results: The most differentially expressed genes in adipocytes of obese individuals consisted of 433 upregulated and 244 downregulated genes. Of these, 410 genes could be classified into 20 functional Gene Ontology categories. The analyses indicated that the inflammation/ immune response category was over-represented, and that most inflammation-related genes were upregulated in adipocytes of obese subjects. Quantitative real-time PCR confirmed the transcriptional upregulation of representative inflammation-related genes (CCL2 and CCL3) encoding the chemokines monocyte chemoattractant protein-1 and macrophage inflammatory protein 1α. The differential expression levels of eight positional candidate genes, including inflammation-related THY1 and C1QTNF5, were also confirmed. These genes are located on chromosome 11q22-q24, a region with linkage to obesity in the Pima Indians. Conclusions/interpretation: This study provides evidence supporting the active role of mature adipocytes in obesityrelated inflammation. It also provides potential candidate genes for susceptibility to obesity.

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“…14 The molecular mechanisms in adipose tissue underlying obesity-related complications are unknown, but may depend on alterations in the lipolytic cascade leading to impaired hormone sensitive lipase activity. 15 However, it is also conceivable that expression of non-hormonally regulated proteins with a role in NEFA metabolism, such as FABPs and CD36, are altered in obesity, hence contributing to the phenotype. Although these proteins have been shown to play important roles in metabolic control in mouse models, to date very little is known about the expression of these proteins in human obesity.…”

Section: Introductionmentioning

confidence: 99%

Effects of obesity and weight loss on the expression of proteins involved in fatty acid metabolism in human adipose tissue

et al. 2002

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OBJECTIVE: Disturbances in adipocyte lipolysis in obesity may contribute to elevated circulating non-esterified fatty acid (NEFA) concentrations and insulin resistance. In experimental models, NEFA metabolism is influenced by adipocyte proteins such as adipocyte and keratinocyte lipid binding proteins (aP2=ALBP and mal1=KLBP) and fatty acid translocase (CD36). We investigated the effect of obesity and weight loss on the expression of these proteins in human subcutaneous adipose tissue. STUDY DESIGN AND SUBJECTS: Subcutaneous adipose tissue was obtained from 12 obese (body mass index (BMI) 42.4 AE 1.6 kg=m 2 ) and 12 lean (23.4 AE 0.6 kg=m 2 ) subjects. The obese subjects underwent gastric banding and biopsies were taken again after 2 y following a significant weight reduction (BMI 32.8 AE 1.4 kg=m 2 ). Adipose tissue proteins were quantified by Western blotting. RESULTS: Differential expression of ALBP, KLBP and CD36 was observed in lean and weight-reduced subjects compared with obese individuals. This resulted in a significantly lower ALBP=KLBP ratio in lean and weight-reduced individuals compared to obese subjects. Furthermore there was a significant influence of gender on this ratio. Moreover, the commonly used internal standard protein actin was expressed significantly higher in lean compared to obese individuals. CONCLUSION: The relative content of ALBP and KLBP in human adipose tissue changes with obesity, weight loss and gender indicating differential regulation. Differing responses in the expression patterns of adipose tissue proteins capable of binding NEFAs in response to weight changes suggest a potential importance in the development of obesity-associated complications.

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Hunting for human obesity genes? Look in the adipose tissue!

Cited by 31 publications

References 21 publications

Obesity and polymorphisms in genes regulating human adipose tissue

Obesity and polymorphisms in genes regulating human adipose tissue

Microarray profiling of isolated abdominal subcutaneous adipocytes from obese vs non-obese Pima Indians: increased expression of inflammation-related genes

Effects of obesity and weight loss on the expression of proteins involved in fatty acid metabolism in human adipose tissue

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