Adipose Gene Expression Prior to Weight Loss Can Differentiate and Weakly Predict Dietary Responders

Mutch, David M.; Temanni, Ramzi; Hénégar, Corneliu; Combes, Florence; Pelloux, Véronique; Holst, Claus; Sørensen, Thorkild I A; Astrup, Arne; Martínez, J. Alfredo; Saris, Wim H. M.; Viguerie, Nathalie; Langin, Dominique; Zucker, Jean-Daniel; Clément, Karine

doi:10.1371/journal.pone.0001344

Cited by 47 publications

(49 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, our results related to mRNA expression of leptin and TNFalpha on subcutaneous adipose tissue, agree with those reported by Bouchard et al [7] and Mutch et al [32], who did not find clear differences in the transcriptomic profile at the beginning of the diet that could help to predict the future weight loss response. In our work, leptin mRNA expression levels were lower in the responder group after dietary treatment, which has been previously described and related with a decrease in leptin plasma levels [40].…”

Section: Discussionsupporting

confidence: 93%

Leptin and TNF-alpha promoter methylation levels measured by MSP could predict the response to a low-calorie diet

et al. 2011

Self Cite

View full text Add to dashboard Cite

Obesity-associated adipose tissue enlargement is characterized by an enhanced proinflammatory status and an elevated secretion of adipokines such as leptin and cytokines such as TNF-alpha. Among the different mechanisms that could underlie the interindividual differences in obesity, epigenetic regulation of gene expression has emerged as a potentially important determinant. Therefore, twenty-seven obese women (age: 32-50 years; baseline Body Mass Index, BMI: 34.4±4.2 Kg/m 2 ) were prescribed an eightweek Low-Calorie-Diet and epigenetic marks were assessed. Baseline and endpoint anthropometric parameters were measured and blood samples were drawn. Genomic DNA and RNA from adipose tissue biopsies were isolated before and after the dietary intervention. Leptin and TNF-alpha promoter methylation were measured by MSP after bisulfite treatment and gene expression was also analyzed.Obese women with a successful weight loss (≥5% of initial body weight, n=21) improved the lipid profile and fat mass percentage (-12%, p<0.05). Both systolic (-5%, p<0.05) and diastolic (-8%, p<0.01) blood pressures significantly decreased. At baseline women with better response to the dietary intervention showed lower promoter methylation levels of leptin (-47%, p<0.05) and TNF-alpha (-39%, p=0.071) than the non-responder group (n=6), while no differences were found between responder and non-responder group in leptin and TNF-alpha gene expression analysis. These data suggest that leptin and TNF-alpha methylation levels could be used as epigenetic biomarkers concerning the response to a Low-CalorieDiet. Indeed, methylation profile could help to predict the susceptibility to weight loss as well as some comorbidities such as hypertension or type 2 diabetes.

show abstract

Section: Discussionsupporting

confidence: 93%

Leptin and TNF-alpha promoter methylation levels measured by MSP could predict the response to a low-calorie diet

et al. 2011

Self Cite

View full text Add to dashboard Cite

show abstract

“…20 An advantage of using direct and swap microarray pairs is the ability to improve the quality of a dataset by filtering and removing data that are dye sensitive, thereby reducing the number of false positives. For each pair of microarrays, expression data that passed this first filter were averaged per probe so as to have a single expression value per probe per microarray pair.…”

Section: Microarray Analysismentioning

confidence: 99%

Using gene expression to predict the secretome of differentiating human preadipocytes

et al. 2009

View full text Add to dashboard Cite

Objective: To characterize the secretome of differentiating human preadipocytes using global gene expression profiling. Design: Gene expression was measured using microarrays at days 0, 1, 3, 5, 7 and 10 in primary preadipocytes undergoing adipogenesis (n ¼ 6 independent subjects). Predictive bioinformatic algorithms were employed to identify those differentially expressed genes that code for secreted proteins. Measurements: Gene expression was assessed using microarrays and real-time reverse transcriptase PCR, bioinformatic predictive algorithms were used to identify the secretome of differentiating preadipocytes, and the secretion of the most significant candidates were confirmed at the protein level using western blots or ELISA tests. Gene expression was also assayed in the adipocyte and stroma vascular fraction (SVF) of obese subjects. Results: Microarray analysis identified 33 genes whose expression significantly changed (false discovery rate of 1%) during adipogenesis and code for secreted proteins. Of these genes, 18 are novel candidate adipose tissue 'secretome' genes. Their relative gene expression in adipocyte and SVF of obese subjects revealed that most of these genes are more highly expressed in the SVF. A novel candidate, matrix gla protein (MGP), was upregulated (B30-fold) during adipogenesis, second only to leptin (B50-fold). MGP and another secretome candidate protein, inhibin beta B (INHBB), were detected in the secretion media of adipocytes isolated from adipose tissue explants. Conclusions: Gene expression coupled with predictive bioinformatic algorithms has proved a valid and alternative approach to further define the adipocyte secretome. Many of the novel candidate secretome genes are components of the coagulation and fibrinolytic systems. MGP and INHBB represent new adipokines whose function in adipose tissue remains to be unravelled.

show abstract

“…Previous attempts to predict an individual's response (ie, high compared with low weight loss) using only scAT 4 gene expression profiles appear to be limited, suggesting that alternate approaches may be required to improve prediction accuracy (18,19).…”

Section: Introductionmentioning

confidence: 99%

A distinct adipose tissue gene expression response to caloric restriction predicts 6-mo weight maintenance in obese subjects

Mutch

Pers

Temanni

et al. 2011

The American Journal of Clinical Nutrition

Self Cite

View full text Add to dashboard Cite

Background: Weight loss has been shown to reduce risk factors associated with cardiovascular disease and diabetes; however, successful maintenance of weight loss continues to pose a challenge. Objective: The present study was designed to assess whether changes in subcutaneous adipose tissue (scAT) gene expression during a low-calorie diet (LCD) could be used to differentiate and predict subjects who experience successful short-term weight maintenance from subjects who experience weight regain. Design: Forty white women followed a dietary protocol consisting of an 8-wk LCD phase followed by a 6-mo weight-maintenance phase. Participants were classified as weight maintainers (WMs; 0-10% weight regain) and weight regainers (WRs; 50-100% weight regain) by considering changes in body weight during the 2 phases. Anthropometric measurements, bioclinical variables, and scAT gene expression were studied in all individuals before and after the LCD. Energy intake was estimated by using 3-d dietary records. Results: No differences in body weight and fasting insulin were observed between WMs and WRs at baseline or after the LCD period. The LCD resulted in significant decreases in body weight and in several plasma variables in both groups. WMs experienced a significant reduction in insulin secretion in response to an oralglucose-tolerance test after the LCD; in contrast, no changes in insulin secretion were observed in WRs after the LCD. An ANOVA of scAT gene expression showed that genes regulating fatty acid metabolism, citric acid cycle, oxidative phosphorylation, and apoptosis were regulated differently by the LCD in WM and WR subjects. Conclusion: This study suggests that LCD-induced changes in insulin secretion and scAT gene expression may have the potential to predict successful short-term weight maintenance. This trial was registered at clinicaltrials.gov as NCT00390637.Am J Clin Nutr 2011;94:1399-409.

show abstract

Adipose Gene Expression Prior to Weight Loss Can Differentiate and Weakly Predict Dietary Responders

Cited by 47 publications

References 33 publications

Leptin and TNF-alpha promoter methylation levels measured by MSP could predict the response to a low-calorie diet

Leptin and TNF-alpha promoter methylation levels measured by MSP could predict the response to a low-calorie diet

Using gene expression to predict the secretome of differentiating human preadipocytes

A distinct adipose tissue gene expression response to caloric restriction predicts 6-mo weight maintenance in obese subjects

Contact Info

Product

Resources

About