Changes in adipose tissue gene expression with energy-restricted diets in obese women1–4,

Dahlman, Ingrid; Linder, Kristina; Nordström, Elisabet Arvidsson; Андерссон, И.; Lidén, Johan; Verdich, Camilla; Sørensen, Thorkild I A; Arner, Peter

doi:10.1093/ajcn/81.6.1275

Cited by 134 publications

(118 citation statements)

References 32 publications

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“…Several recent studies have examined how nutrition affects gene expression in the context of obesity and metabolic syndrome (40,41). These investigations (the FUNGENUT study) profiled gene expression in subcutaneous adipose tissue and found downregulation of IGF pathway genes and genes related to fat metabolism.…”

Section: Discussionmentioning

confidence: 99%

Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention

Ornish

Magbanua

Weidner

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

261

152

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Epidemiological and prospective studies indicate that comprehensive lifestyle changes may modify the progression of prostate cancer. However, the molecular mechanisms by which improvements in diet and lifestyle might affect the prostate microenvironment are poorly understood. We conducted a pilot study to examine changes in prostate gene expression in a unique population of men with low-risk prostate cancer who declined immediate surgery, hormonal therapy, or radiation and participated in an intensive nutrition and lifestyle intervention while undergoing careful surveillance for tumor progression. Consistent with previous studies, significant improvements in weight, abdominal obesity, blood pressure, and lipid profile were observed (all P < 0.05), and surveillance of low-risk patients was safe. Gene expression profiles were obtained from 30 participants, pairing RNA samples from control prostate needle biopsy taken before intervention to RNA from the same patient's 3-month postintervention biopsy. Quantitative real-time PCR was used to validate array observations for selected transcripts. Two-class paired analysis of global gene expression using significance analysis of microarrays detected 48 up-regulated and 453 down-regulated transcripts after the intervention. Pathway analysis identified significant modulation of biological processes that have critical roles in tumorigenesis, including protein metabolism and modification, intracellular protein traffic, and protein phosphorylation (all P < 0.05). Intensive nutrition and lifestyle changes may modulate gene expression in the prostate. Understanding the prostate molecular response to comprehensive lifestyle changes may strengthen efforts to develop effective prevention and treatment. Larger clinical trials are warranted to confirm the results of this pilot study.exercise ͉ lifestyle changes ͉ prostate cancer ͉ SHOC2 ͉ stress management E pidemiological evidence (1, 2) and migrant studies (3) indicate that the incidence of clinically significant prostate cancer is much lower in parts of the world where people eat a predominantly low-fat, plant-based diet. We (4, 5) and others (6) have shown previously that diet and lifestyle interventions in men with earlystage prostate cancer decrease prostate-specific antigen (PSA) and decrease the rate of PSA increase. These studies provided some evidence that comprehensive lifestyle changes may have therapeutic potential in early prostate cancers. However, although these interventions are associated with decreased circulating insulin-like growth factor 1 (IGF1) (7), and although serum from men after intervention has reduced the ability to stimulate prostate cell-line growth in vitro (4), the actual molecular effects of these interventions in prostate tissue have not been previously examined.Many men with indolent prostate cancers detected by PSA screening will not exhibit disease progression during their lifetime; their treatment and associated side effects are unnecessary (8). We report here the results of the Gene Expressio...

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Section: Discussionmentioning

confidence: 99%

Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention

Ornish

Magbanua

Weidner

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

261

152

View full text Add to dashboard Cite

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“…One such identified obesity candidate gene is CIDEA. 4,5 Of course, there are limits to the usefulness of the microarray approach for identifying adipose genes of importance for obesity. For genes differentially expressed between case and control cohorts, we cannot differentiate between what is primary cause and what is secondary association; one consistent finding is upregulation of inflammatory genes in adipose tissue of obese humans, which intuitively is of greater importance for the metabolic complications of obesity than for obesity per se.…”

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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“…[19][20][21][22][23] A few studies have applied microarray technologies to study gene expression in AT of massively obese subjects either in comparison to lean subjects cross-sectionally 24,25 or after short-term weight reduction. 26,27 These studies have demonstrated downregulation in the expression of genes involved in inflammation and desaturation of fatty acids. 26,27 In the present work, we studied the effect of long-term weight reduction on gene expression in AT of overweight or obese individuals with impaired fasting glycemia or impaired glucose tolerance and other features of the metabolic syndrome.…”

Section: Introductionmentioning

confidence: 99%

“…26,27 These studies have demonstrated downregulation in the expression of genes involved in inflammation and desaturation of fatty acids. 26,27 In the present work, we studied the effect of long-term weight reduction on gene expression in AT of overweight or obese individuals with impaired fasting glycemia or impaired glucose tolerance and other features of the metabolic syndrome. We aimed to examine the effect of the long-term moderate weight reduction on gene expression in AT and to identify genes and gene clusters responsive to treatment and thereby likely contributing to the development of the metabolic syndrome.…”

Section: Introductionmentioning

confidence: 99%

Weight reduction modulates expression of genes involved in extracellular matrix and cell death: the GENOBIN study

et al. 2007

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Objective: Lifestyle and genetic factors interact in the development of obesity and the metabolic syndrome. The molecular mechanisms underlying the beneficial dietary modifications are, however, unclear. We aimed to examine the effect of the longterm moderate weight reduction on gene expression in adipose tissue (AT) and to identify genes and gene clusters responsive to treatment and thereby likely contributing to the development of the metabolic syndrome. Design: Randomized controlled and individualized weight reduction intervention. Subjects: Forty-six subjects with impaired fasting glycemia or impaired glucose tolerance and features of metabolic syndrome, aged 6077 years were randomized either to a weight reduction (WR) (n ¼ 28) or a control (n ¼ 18) group lasting for 33 weeks. Measurements: Oral and intravenous glucose tolerance tests and subcutaneous AT biopsies were performed before and after the intervention. Gene expression of AT was studied using microarray technology in subgroups of WR (with weight reduction X5%, n ¼ 9) and control group (n ¼ 10). The results were confirmed using quantitative PCR. Results: In the WR group, glucose metabolism improved. Moreover, an inverse correlation between the change in S I and the change in body weight was found (r ¼ À0.44, P ¼ 0.026). Downregulation of gene expression (Po0.01) involving gene ontology groups of extracellular matrix and cell death was seen. Such changes did not occur in the control group. The tenomodulin-gene was one of the most downregulated genes (À39716%, Po0.0001). Moreover, its expression correlated with insulin sensitivity (r ¼ À0.34, P ¼ 0.005) before the intervention and with body adiposity both before (r ¼ 0.42, P ¼ 0.007) and after (r ¼ 0.30, P ¼ 0.056) the intervention. Conclusion: Genes regulating the extracellular matrix and cell death showed a strong downregulation after long-term weight reduction. This likely reflects a new stable state at the molecular level in AT. Further studies are warranted to elucidate the mechanisms of these genetic factors.

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Changes in adipose tissue gene expression with energy-restricted diets in obese women1–4,

Abstract: Macronutrients have a secondary role in changes in adipocyte gene expression after energy-restricted diets. The most striking alteration after energy restriction is a coordinated reduction in the expression of genes regulating the production of polyunsaturated fatty acids.

Cited by 134 publications

References 32 publications

Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention

Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention

Obesity and polymorphisms in genes regulating human adipose tissue

Weight reduction modulates expression of genes involved in extracellular matrix and cell death: the GENOBIN study

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