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System model network for adipose tissue signatures related to weight changes in response to calorie restriction and subsequent weight maintenance.

Montastier E, Villa-Vialaneix N, Caspar-Bauguil S, Hlavaty P, Tvrzicka E, Gonzalez I, Saris WH, Langin D, Kunesova M, Viguerie N - PLoS Comput. Biol. (2015)

Bottom Line: The resulting networks were analyzed using node clustering, systematic important node extraction and cluster comparisons.By contrast, after LCD a strong positive relationship between AT myristoleic acid (a fatty acid with low AT level) content and de novo lipogenesis mRNAs was found.This original system biology approach provides novel insight in the AT response to weight control by highlighting the central role of myristoleic acid that may account for the beneficial effects of weight loss.

View Article: PubMed Central - PubMed

Affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases (I2MC), Toulouse, France; University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France; Toulouse University Hospitals, Departments of Clinical Biochemistry and Nutrition, Toulouse, France.

ABSTRACT
Nutrigenomics investigates relationships between nutrients and all genome-encoded molecular entities. This holistic approach requires systems biology to scrutinize the effects of diet on tissue biology. To decipher the adipose tissue (AT) response to diet induced weight changes we focused on key molecular (lipids and transcripts) AT species during a longitudinal dietary intervention. To obtain a systems model, a network approach was used to combine all sets of variables (bio-clinical, fatty acids and mRNA levels) and get an overview of their interactions. AT fatty acids and mRNA levels were quantified in 135 obese women at baseline, after an 8-week low calorie diet (LCD) and after 6 months of ad libitum weight maintenance diet (WMD). After LCD, individuals were stratified a posteriori according to weight change during WMD. A 3 steps approach was used to infer a global model involving the 3 sets of variables. It consisted in inferring intra-omic networks with sparse partial correlations and inter-omic networks with regularized canonical correlation analysis and finally combining the obtained omic-specific network in a single global model. The resulting networks were analyzed using node clustering, systematic important node extraction and cluster comparisons. Overall, AT showed both constant and phase-specific biological signatures in response to dietary intervention. AT from women regaining weight displayed growth factors, angiogenesis and proliferation signaling signatures, suggesting unfavorable tissue hyperplasia. By contrast, after LCD a strong positive relationship between AT myristoleic acid (a fatty acid with low AT level) content and de novo lipogenesis mRNAs was found. This relationship was also observed, after WMD, in the group of women that continued to lose weight. This original system biology approach provides novel insight in the AT response to weight control by highlighting the central role of myristoleic acid that may account for the beneficial effects of weight loss.

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Flowchart for individuals’ selection from the DiOGenes cohort.Participants entering subsequent phases of the study as well as dropouts are indicated in total. AT, adipose tissue; CID, clinical investigation day; FA, fatty acids; HGI, high glycemic index; HP, high protein content; LCD, low calorie diet; LGI, low glycemic index; LP, low protein content; WMD, weight maintenance diet.
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pcbi.1004047.g001: Flowchart for individuals’ selection from the DiOGenes cohort.Participants entering subsequent phases of the study as well as dropouts are indicated in total. AT, adipose tissue; CID, clinical investigation day; FA, fatty acids; HGI, high glycemic index; HP, high protein content; LCD, low calorie diet; LGI, low glycemic index; LP, low protein content; WMD, weight maintenance diet.

Mentions: Study design. The data presented in this paper are part of those collected during the DiOGenes study (contact information at www.diogenes-eu.org) The DiOGenes project investigated the effects of diets with different content of protein and glycemic index on weight-loss maintenance and metabolic and cardiovascular risk factors after a phase of calorie restriction, in obese/overweight individuals. The trial protocol and supporting CONSORT checklist are available as supporting information; see S1 Protocol and S1 Checklist. Healthy overweight (body mass index (BMI) ≥27 kg/m2) individuals, aged <65 years were eligible for the study. Exclusion criteria were BMI 45 kg/m2, liver or kidney diseases, cardiovascular diseases, diabetes mellitus (type 1 or type 2), special diets/eating disorders, systemic infections/chronic diseases, cancer within the last 10 years, weight change >3 kg within the previous 3 months, and other clinical disorders or use of prescription medication that might interfere with the outcome of the study. A detailed description of inclusion and exclusion criteria has been published previously [20]. BMI was calculated by dividing weight in kilograms by the square of height in meters. Waist circumference was measured between the bottom of the ribs and the top of the hip bone. A detailed description of the DiOGenes intervention trial and main outcomes can be found in previous core publications [20–22]. Briefly, after the first clinical investigation day (baseline), eligible individuals followed an active weight loss phase of 8-week low calorie (3.3–4.2 MJ/d) diet (LCD) using commercial meal replacements (Modifast, Nutrition et Santé). The individuals with ≥ 8% of initial body weight loss during LCD were randomized into one of five ad libitum weight maintenance diets (WMD) for 6 months: 4 diets combining high and low protein content with high and low glycemic index of carbohydrates, and a control low fat (25–30% energy) diet according to National dietary guidelines on healthy diets [22]. During WMD, the individuals were provided dietary instruction as described in [22]. Dietary intake was assessed at screening, 4 weeks after the beginning and at the end of WMD. The subjects were asked to complete a 3-day weighed food record, including 2-week days and 1 weekend day. Dietary records were validated by a nutritionist. Clinical investigations including anthropometric measures (height, weight, waist circumference, body composition), blood pressure measurements, fasting blood sampling, and subcutaneous AT biopsies were performed at baseline (BAS) and at the end of each phase. All procedures were standardized between the 8 study centers across Europe [21]. Fig. 1 displays the organizational flowchart through the trial protocol and the individuals’ selection from the DiOGenes cohort for the present study.


System model network for adipose tissue signatures related to weight changes in response to calorie restriction and subsequent weight maintenance.

Montastier E, Villa-Vialaneix N, Caspar-Bauguil S, Hlavaty P, Tvrzicka E, Gonzalez I, Saris WH, Langin D, Kunesova M, Viguerie N - PLoS Comput. Biol. (2015)

Flowchart for individuals’ selection from the DiOGenes cohort.Participants entering subsequent phases of the study as well as dropouts are indicated in total. AT, adipose tissue; CID, clinical investigation day; FA, fatty acids; HGI, high glycemic index; HP, high protein content; LCD, low calorie diet; LGI, low glycemic index; LP, low protein content; WMD, weight maintenance diet.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4295881&req=5

pcbi.1004047.g001: Flowchart for individuals’ selection from the DiOGenes cohort.Participants entering subsequent phases of the study as well as dropouts are indicated in total. AT, adipose tissue; CID, clinical investigation day; FA, fatty acids; HGI, high glycemic index; HP, high protein content; LCD, low calorie diet; LGI, low glycemic index; LP, low protein content; WMD, weight maintenance diet.
Mentions: Study design. The data presented in this paper are part of those collected during the DiOGenes study (contact information at www.diogenes-eu.org) The DiOGenes project investigated the effects of diets with different content of protein and glycemic index on weight-loss maintenance and metabolic and cardiovascular risk factors after a phase of calorie restriction, in obese/overweight individuals. The trial protocol and supporting CONSORT checklist are available as supporting information; see S1 Protocol and S1 Checklist. Healthy overweight (body mass index (BMI) ≥27 kg/m2) individuals, aged <65 years were eligible for the study. Exclusion criteria were BMI 45 kg/m2, liver or kidney diseases, cardiovascular diseases, diabetes mellitus (type 1 or type 2), special diets/eating disorders, systemic infections/chronic diseases, cancer within the last 10 years, weight change >3 kg within the previous 3 months, and other clinical disorders or use of prescription medication that might interfere with the outcome of the study. A detailed description of inclusion and exclusion criteria has been published previously [20]. BMI was calculated by dividing weight in kilograms by the square of height in meters. Waist circumference was measured between the bottom of the ribs and the top of the hip bone. A detailed description of the DiOGenes intervention trial and main outcomes can be found in previous core publications [20–22]. Briefly, after the first clinical investigation day (baseline), eligible individuals followed an active weight loss phase of 8-week low calorie (3.3–4.2 MJ/d) diet (LCD) using commercial meal replacements (Modifast, Nutrition et Santé). The individuals with ≥ 8% of initial body weight loss during LCD were randomized into one of five ad libitum weight maintenance diets (WMD) for 6 months: 4 diets combining high and low protein content with high and low glycemic index of carbohydrates, and a control low fat (25–30% energy) diet according to National dietary guidelines on healthy diets [22]. During WMD, the individuals were provided dietary instruction as described in [22]. Dietary intake was assessed at screening, 4 weeks after the beginning and at the end of WMD. The subjects were asked to complete a 3-day weighed food record, including 2-week days and 1 weekend day. Dietary records were validated by a nutritionist. Clinical investigations including anthropometric measures (height, weight, waist circumference, body composition), blood pressure measurements, fasting blood sampling, and subcutaneous AT biopsies were performed at baseline (BAS) and at the end of each phase. All procedures were standardized between the 8 study centers across Europe [21]. Fig. 1 displays the organizational flowchart through the trial protocol and the individuals’ selection from the DiOGenes cohort for the present study.

Bottom Line: The resulting networks were analyzed using node clustering, systematic important node extraction and cluster comparisons.By contrast, after LCD a strong positive relationship between AT myristoleic acid (a fatty acid with low AT level) content and de novo lipogenesis mRNAs was found.This original system biology approach provides novel insight in the AT response to weight control by highlighting the central role of myristoleic acid that may account for the beneficial effects of weight loss.

View Article: PubMed Central - PubMed

Affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases (I2MC), Toulouse, France; University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France; Toulouse University Hospitals, Departments of Clinical Biochemistry and Nutrition, Toulouse, France.

ABSTRACT
Nutrigenomics investigates relationships between nutrients and all genome-encoded molecular entities. This holistic approach requires systems biology to scrutinize the effects of diet on tissue biology. To decipher the adipose tissue (AT) response to diet induced weight changes we focused on key molecular (lipids and transcripts) AT species during a longitudinal dietary intervention. To obtain a systems model, a network approach was used to combine all sets of variables (bio-clinical, fatty acids and mRNA levels) and get an overview of their interactions. AT fatty acids and mRNA levels were quantified in 135 obese women at baseline, after an 8-week low calorie diet (LCD) and after 6 months of ad libitum weight maintenance diet (WMD). After LCD, individuals were stratified a posteriori according to weight change during WMD. A 3 steps approach was used to infer a global model involving the 3 sets of variables. It consisted in inferring intra-omic networks with sparse partial correlations and inter-omic networks with regularized canonical correlation analysis and finally combining the obtained omic-specific network in a single global model. The resulting networks were analyzed using node clustering, systematic important node extraction and cluster comparisons. Overall, AT showed both constant and phase-specific biological signatures in response to dietary intervention. AT from women regaining weight displayed growth factors, angiogenesis and proliferation signaling signatures, suggesting unfavorable tissue hyperplasia. By contrast, after LCD a strong positive relationship between AT myristoleic acid (a fatty acid with low AT level) content and de novo lipogenesis mRNAs was found. This relationship was also observed, after WMD, in the group of women that continued to lose weight. This original system biology approach provides novel insight in the AT response to weight control by highlighting the central role of myristoleic acid that may account for the beneficial effects of weight loss.

Show MeSH
Related in: MedlinePlus