Context: While calorie restriction has proven beneficial for weight loss, long-term weight control is variable between individuals.

Objective: To identify biomarkers of successful weight control during a dietary intervention (DI).

Design, Setting, and Participants: Adipose tissue (AT) transcriptomes were compared between 21 obese individuals that either maintained weight loss or regained weight during the DI. Results were validated on 310 individuals from the same study using RT-qPCR, and protein levels of potential circulating biomarkers measured by ELISA.

Intervention: Individuals underwent 8-weeks of low-calorie diet, then 6-months of ad libitum diet.

Outcome Measure: Weight changes at the end of DI.

Results: We evaluated 6 genes that had altered expression during DI, encode secreted proteins, and have not previously been implicated in weight control (EGFL6, FSTL3, CRYAB, TNMD, SPARC, IGFBP3); as well as genes for which baseline expression was different between those with good and poor weight control (ASPN, USP53). Changes in plasma concentration of EGFL6, FSTL3 and CRYAB mirrored AT mRNA expression, all decreased during DI in individuals with good weight control. ASPN and USP53 had higher baseline expression in individuals that went on to have good weight control. eQTL analysis found polymorphisms associated with expression levels of USP53 in AT. A regulatory network was identified in which TGFβ1 was responsible for down-regulation of certain genes during DI in good-controllers. Interestingly, ASPN is a TGFβ1 inhibitor.

Conclusions: We found circulating biomarkers associated with weight control, which could influence weight management strategies, and genes that may be prognostic for successful weight control.