title: Weight reduction modulates expression of genes involved in extracellular matrix and cell death: the GENOBIN study.
abstract: OBJECTIVE
  Lifestyle and genetic factors interact in the development of obesity and the metabolic syndrome. The molecular mechanisms underlying the beneficial dietary modifications are, however, unclear. We aimed to examine the effect of the long-term moderate weight reduction on gene expression in adipose tissue (AT) and to identify genes and gene clusters responsive to treatment and thereby likely contributing to the development of the metabolic syndrome.
  
  
  METHODS
  Randomized controlled and individualized weight reduction intervention.
  
  
  METHODS
  Forty-six subjects with impaired fasting glycemia or impaired glucose tolerance and features of metabolic syndrome, aged 60+/-7 years were randomized either to a weight reduction (WR) (n=28) or a control (n=18) group lasting for 33 weeks.
  
  
  METHODS
  Oral and intravenous glucose tolerance tests and subcutaneous AT biopsies were performed before and after the intervention. Gene expression of AT was studied using microarray technology in subgroups of WR (with weight reduction > or =5%, n=9) and control group (n=10). The results were confirmed using quantitative PCR.
  
  
  RESULTS
  In the WR group, glucose metabolism improved. Moreover, an inverse correlation between the change in S (I) and the change in body weight was found (r=-0.44, P=0.026). Downregulation of gene expression (P<0.01) involving gene ontology groups of extracellular matrix and cell death was seen. Such changes did not occur in the control group. The tenomodulin-gene was one of the most downregulated genes (-39+/-16%, P<0.0001). Moreover, its expression correlated with insulin sensitivity (r=-0.34, P=0.005) before the intervention and with body adiposity both before (r=0.42, P=0.007) and after (r=0.30, P=0.056) the intervention.
  
  
  CONCLUSIONS
  Genes regulating the extracellular matrix and cell death showed a strong downregulation after long-term weight reduction. This likely reflects a new stable state at the molecular level in AT. Further studies are warranted to elucidate the mechanisms of these genetic factors.
authors.affiliation: School of Public Health and Clinical Nutrition, Clinical Nutrition and Food and Health Research Center, University of Kuopio, Kuopio, Finland. marjukka.kolehmainen@uku.fi
authors.forename: M
authors.initials: M
authors.lastname: Kolehmainen
authors.forename: T
authors.initials: T
authors.lastname: Salopuro
authors.forename: U S
authors.initials: US
authors.lastname: Schwab
authors.forename: J
authors.initials: J
authors.lastname: Kekäläinen
authors.forename: P
authors.initials: P
authors.lastname: Kallio
authors.forename: D E
authors.initials: DE
authors.lastname: Laaksonen
authors.forename: L
authors.initials: L
authors.lastname: Pulkkinen
authors.forename: V I
authors.initials: VI
authors.lastname: Lindi
authors.forename: K
authors.initials: K
authors.lastname: Sivenius
authors.forename: U
authors.initials: U
authors.lastname: Mager
authors.forename: N
authors.initials: N
authors.lastname: Siitonen
authors.forename: L
authors.initials: L
authors.lastname: Niskanen
authors.forename: H
authors.initials: H
authors.lastname: Gylling
authors.forename: R
authors.initials: R
authors.lastname: Rauramaa
authors.forename: M
authors.initials: M
authors.lastname: Uusitupa
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D016022:Case-Control Studies; D016923:Cell Death / Q000235:genetics; D005109:Extracellular Matrix / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000178:diet therapy / Q000235:genetics*; D015431:Weight Loss / Q000235:genetics*
chemical_list: D001786:Blood Glucose; D007328:Insulin