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.
Highlights
The main function of adipose tissue (AT) is to store excess energy as triglycerides and to release non-esterified fatty acids (FAs) for other tissues during periods of energy demand
Obesity is an excess fat mass leading to metabolic diseases
In the form of esterified fatty acids, and secretory organ, the adipose tissue has a pivotal role in obesity and its related complications
Summary
The main function of adipose tissue (AT) is to store excess energy as triglycerides and to release non-esterified fatty acids (FAs) for other tissues during periods of energy demand. AT expansion results in dysfunctional non-esterified FA release and imbalance in production of anti/pro-inflammatory mediators [4]. Most of the obesity-related metabolic disturbances are reversible with weight loss [5]. Weight fluctuations are frequent since individuals involved in dieting-induced weight loss are often unsuccessful at long last [6, 7]. Adaptations occurring in AT during dietary weight management programs remain unclear especially regarding weight control after dieting [8]. Studies on FA composition of AT during weight control trials are scarce [9, 10]. Low 16:1(cis-9) (palmitoleic acid) and 14:1(cis-9) (myristoleic acid) may predict favorable weight control outcome [11]
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