Molecular Biomarkers for Weight Control in Obese Individuals Subjected to a Multiphase Dietary Intervention

J Clin Endocrinol Metab. 2017 Aug 1;102(8):2751-2761. doi: 10.1210/jc.2016-3997.

Abstract

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 enzyme-linked 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 those with good and poor weight control (ASPN, USP53). Changes in plasma concentrations of EGFL6, FSTL3, and CRYAB mirrored AT messenger 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 in which 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.

Trial registration: ClinicalTrials.gov NCT00390637.

MeSH terms

  • Adult
  • Biomarkers / metabolism
  • Calcium-Binding Proteins
  • Caloric Restriction*
  • Cell Adhesion Molecules
  • Down-Regulation
  • Enzyme-Linked Immunosorbent Assay
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism
  • Female
  • Follistatin-Related Proteins / genetics
  • Follistatin-Related Proteins / metabolism
  • Gene Expression Profiling
  • Gene Regulatory Networks
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / genetics
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Microarray Analysis
  • Middle Aged
  • Obesity / diet therapy*
  • Obesity / genetics
  • Obesity / metabolism
  • Osteonectin / genetics
  • Osteonectin / metabolism
  • Polymorphism, Genetic
  • Quantitative Trait Loci
  • RNA, Messenger / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Subcutaneous Fat / metabolism*
  • Transforming Growth Factor beta1 / metabolism
  • Ubiquitin-Specific Proteases / genetics
  • Ubiquitin-Specific Proteases / metabolism
  • alpha-Crystallin B Chain / genetics
  • alpha-Crystallin B Chain / metabolism

Substances

  • ASPN protein, human
  • Biomarkers
  • CRYAB protein, human
  • Calcium-Binding Proteins
  • Cell Adhesion Molecules
  • EGFL6 protein, human
  • Extracellular Matrix Proteins
  • Follistatin-Related Proteins
  • Fstl3 protein, human
  • IGFBP3 protein, human
  • Insulin-Like Growth Factor Binding Protein 3
  • Membrane Glycoproteins
  • Membrane Proteins
  • Osteonectin
  • RNA, Messenger
  • SPARC protein, human
  • TGFB1 protein, human
  • TNMD protein, human
  • Transforming Growth Factor beta1
  • alpha-Crystallin B Chain
  • USP53 protein, human
  • Ubiquitin-Specific Proteases

Associated data

  • ClinicalTrials.gov/NCT00390637