title: Adipose tissue gene expression is differentially regulated with different rates of weight loss in overweight and obese humans.
abstract: Moderate weight loss (WL) can ameliorate adverse health effects associated with obesity, reflected by an improved adipose tissue (AT) gene expression profile. However, the effect of rate of WL on the AT transcriptome is unknown. We investigated the global AT gene expression profile before and after two different rates of WL that resulted in similar total WL, and after a subsequent weight stabilization period.
  
  
  
  In this randomized controlled trial, 25 male and 28 female individuals (body mass index (BMI): 28-35 kg m-2) followed either a low-calorie diet (LCD; 1250 kcal day-1) for 12 weeks or a very-low-calorie diet (VLCD; 500 kcal day-1) for 5 weeks (WL period) and a subsequent weight stable (WS) period of 4 weeks. The WL period and WS period together is termed dietary intervention (DI) period. Abdominal subcutaneous AT biopsies were collected for microarray analysis and gene expression changes were calculated for all three periods in the LCD group, VLCD group and between diets (ΔVLCD-ΔLCD).
  
  
  
  WL was similar between groups during the WL period (LCD: -8.1±0.5 kg, VLCD: -8.9±0.4 kg, difference P=0.25). Overall, more genes were significantly regulated and changes in gene expression appeared more pronounced in the VLCD group compared with the LCD group. Gene sets related to mitochondrial function, adipogenesis and immunity/inflammation were more strongly upregulated on a VLCD compared with a LCD during the DI period (positive ΔVLCD-ΔLCD). Neuronal and olfactory-related gene sets were decreased during the WL period and DI period in the VLCD group.
  
  
  
  The rate of WL (LCD vs VLCD), with similar total WL, strongly regulates AT gene expression. Increased mitochondrial function, angiogenesis and adipogenesis on a VLCD compared with a LCD reflect potential beneficial diet-induced changes in AT, whereas differential neuronal and olfactory regulation suggest functions of these genes beyond the current paradigm.
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: N J
authors.initials: NJ
authors.lastname: Roumans
authors.affiliation: Nutrition, Metabolism and Genomics, Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Fazelzadeh
authors.affiliation: Maastricht Centre for Systems Biology (MaCSBio), Maastricht University, Maastricht, The Netherlands.
authors.forename: S H K
authors.initials: SH
authors.lastname: Tareen
authors.affiliation: Nutrition, Metabolism and Genomics, Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: M V
authors.initials: MV
authors.lastname: Boekschoten
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
authors.initials: EC
authors.lastname: Mariman
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D050156:Adipogenesis; D031204:Caloric Restriction; D004038:Diet, Reducing; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000503:physiopathology*; D050177:Overweight / Q000235:genetics* / Q000503:physiopathology*; D050507:Subcutaneous Fat, Abdominal / Q000378:metabolism*; D046888:Tissue Array Analysis; D015431:Weight Loss / Q000235:genetics* / Q000502:physiology