Molecular biomarkers for weight control in obese individuals subjected to a multi-phase dietary intervention

TY - JOUR

T1 - Molecular biomarkers for weight control in obese individuals subjected to a multi-phase dietary intervention

AU - Bolton, Jennifer L

AU - Montastier, Emilie

AU - Carayol, Jérôme

AU - Bonnel, Sophie

AU - Mir, Lucile

AU - Marques, Marie-Adeline

AU - Astrup, Arne

AU - Saris, Wim H.

AU - Iacovoni, Jason S

AU - Villa-Vialaneix, Nathalie

AU - Valsesia, Armand

AU - Langin, Dominique

AU - Viguerie, Nathalie

N1 - CURIS 2017 NEXS 190

PY - 2017/8/1

Y1 - 2017/8/1

N2 - Context: Although 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 who either maintained weight loss or regained weight during the DI. Results were validated on 310 individuals from the same study using quantitative reverse transcription polymerase chain reaction and protein levels of potential circulating biomarkers measured by enzymelinked immunosorbent assay. Intervention: Individuals underwent 8 weeks of low-calorie diet, then 6 months of ad libitum diet. Outcome Measure: Weight changes at the end of the DI. Results: We evaluated six 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 differed between thosewith good and poorweight control (ASPN, USP53). Changes in plasma concentrations of EGFL6, FSTL3, and CRYAB mirrored ATmessenger RNA expression; all decreased during DI in individuals with good weight control. ASPN and USP53 had higher baseline expression in individuals who went on to have good weight control. Expression quantitative trait loci analysis found polymorphisms associated with expression levels of USP53 in AT. A regulatory network was identified inwhich transforming growth factor β1 (TGF-β1) was responsible for downregulation of certain genes during DI in good controllers. Interestingly, ASPN is a TGF-β1 inhibitor. Conclusions: We found circulating biomarkers associated with weight control that could influence weight management strategies and genes that may be prognostic for successful weight control.

AB - Context: Although 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 who either maintained weight loss or regained weight during the DI. Results were validated on 310 individuals from the same study using quantitative reverse transcription polymerase chain reaction and protein levels of potential circulating biomarkers measured by enzymelinked immunosorbent assay. Intervention: Individuals underwent 8 weeks of low-calorie diet, then 6 months of ad libitum diet. Outcome Measure: Weight changes at the end of the DI. Results: We evaluated six 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 differed between thosewith good and poorweight control (ASPN, USP53). Changes in plasma concentrations of EGFL6, FSTL3, and CRYAB mirrored ATmessenger RNA expression; all decreased during DI in individuals with good weight control. ASPN and USP53 had higher baseline expression in individuals who went on to have good weight control. Expression quantitative trait loci analysis found polymorphisms associated with expression levels of USP53 in AT. A regulatory network was identified inwhich transforming growth factor β1 (TGF-β1) was responsible for downregulation of certain genes during DI in good controllers. Interestingly, ASPN is a TGF-β1 inhibitor. Conclusions: We found circulating biomarkers associated with weight control that could influence weight management strategies and genes that may be prognostic for successful weight control.

KW - Journal Article

U2 - 10.1210/jc.2016-3997

DO - 10.1210/jc.2016-3997

M3 - Journal article

C2 - 28482007

SN - 0021-972X

VL - 102

SP - 2751

EP - 2761

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 8

ER -