title: Weight loss-induced cellular stress in subcutaneous adipose tissue and the risk for weight regain in overweight and obese adults.
abstract: Weight loss is often followed by weight regain after the dietary intervention (DI). Cellular stress is increased in adipose tissue of obese individuals. However, the relation between cellular stress and weight regain is unclear. Previously, we observed increased adipose tissue cellular stress of participants regaining weight compared with participants maintaining weight loss. In the current study, we further investigated the relation between weight regain and changes in the expression of stress-related genes and stress protein levels to determine possible predictors of weight regain.
  
  
  
  In this randomized controlled trial, sixty-one healthy overweight/obese participants followed a DI of either a 5-week very-low-calorie diet (500 kcal per day) or a 12-week low-calorie diet (1250 kcal per day; WL period) with a subsequent 4-week weight stable diet (WS period), and a 9-month follow-up. The WL and WS period taken together was named the DI. Abdominal subcutaneous adipose tissue biopsies were collected in 53 participants for microarray and liquid chromatography-mass spectrometry analysis. RNA and protein levels for a broad set of stress-related genes were correlated to the weight regain percentage.
  
  
  
  Different gene sets correlated to weight regain percentage during WS and DI. Bioinformatics clustering suggests that during the WS phase-defined genes for actin filament dynamics, glucose handling and nutrient sensing are related to weight regain. HIF-1 (hypoxia-inducible factor-1) is indicated as an important regulator. With regard to DI, clustering of correlated genes indicate that LGALS1, ENO1 and ATF2 are important nodes for conferring risk for weight regain.
  
  
  
  Our present findings indicate that the risk for weight regain is related to expression changes of distinct sets of stress-related genes during the first 4 weeks after returning to energy balance, and during the DI. Further research is required to investigate the mechanistic significance of these findings and find targets for preventing weight regain.
authors.affiliation: Department of Human Biology, NUTRIM, School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: N J T
authors.initials: NJT
authors.lastname: Roumans
authors.affiliation: Department of Human Biology, NUTRIM, School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: R G
authors.initials: RG
authors.lastname: Vink
authors.affiliation: Department of Human Biology, NUTRIM, School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: F G
authors.initials: FG
authors.lastname: Bouwman
authors.affiliation: Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Fazelzadeh
authors.affiliation: Department of Human Biology, NUTRIM, School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: M A
authors.initials: MA
authors.lastname: van Baak
authors.affiliation: Department of Human Biology, NUTRIM, School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: E C M
authors.initials: ECM
authors.lastname: Mariman
mesh_terms: D051698:Activating Transcription Factor 2; D017667:Adipocytes / Q000378:metabolism*; D000328:Adult; D014408:Biomarkers, Tumor; D000068959:Body Weight Maintenance / Q000502:physiology*; D031204:Caloric Restriction; D019295:Computational Biology; D004268:DNA-Binding Proteins; D004734:Energy Metabolism; D005260:Female; D037483:Galectin 1; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008297:Male; D009765:Obesity / Q000178:diet therapy* / Q000235:genetics / Q000378:metabolism; D050177:Overweight / Q000378:metabolism / Q000503:physiopathology*; D018384:Oxidative Stress / Q000502:physiology*; D010751:Phosphopyruvate Hydratase; D050507:Subcutaneous Fat, Abdominal / Q000378:metabolism*; D025521:Tumor Suppressor Proteins; D015430:Weight Gain / Q000502:physiology; D015431:Weight Loss / Q000502:physiology*
chemical_list: C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D037483:Galectin 1; C445499:LGALS1 protein, human; D025521:Tumor Suppressor Proteins; C095157:ENO1 protein, human; D010751:Phosphopyruvate Hydratase