title: Changes in fat mass influence SREBP-1c and UCP-2 gene expression in formerly obese subjects.
abstract: OBJECTIVE
  To investigate the effect of fat mass (FM) reduction on adipose tissue gene expression in terms of lipid synthesis [sterol regulatory binding protein 1c (SREBP-1c)] and lipid oxidation [uncoupling protein 2 (UCP-2)] 2 years after lipid malabsorption and to assess the influence of lipid malabsorption on fat-free mass (FFM) maintenance evaluating the expression of genes related to glycolysis [hexokinase (HKII)] and glucose storage [glycogen synthase (GS)].
  
  
  METHODS
  SREBP-1c, UCP-2, HKII, and GS mRNA expression were studied by reverse transcriptase-competitive polymerase chain reaction in 10 massively obese subjects before and 2 years after bilio-pancreatic diversion (BPD). Body composition was assessed by isotopic dilution method and insulin sensitivity by euglycemic-hyperinsulinemic clamp.
  
  
  RESULTS
  FM decrease was approximately 60%, whereas FFM remained at normal physiological levels. In adipose tissue, SREBP-1c mRNA reduction (-39%, p < 0.005) was related only to FM changes after BPD, and UCP-2 decrease (-37%, p < 0.05) was dependent on free fatty acid (FFA) changes. No significant variations were observed in HKII and GS gene expression in skeletal muscle.
  
  
  CONCLUSIONS
  Lipid malabsorption induced by BPD altered the expression of genes involved in glucose and lipid metabolism, with different consequences on FM and FFM. The degree of FM loss seems to interfere with SREBP-1c gene suppression to preserve an adequate amount of fat storage, in accordance with the thrifty genotype hypothesis. The reduction of FFAs induced by BPD acts in inhibiting FFA transportation to the mitochondria (UCP-2), contributing to the decreased lipid oxidation inside the adipose tissue.
authors.affiliation: Department of Internal Medicine, Catholic University of the Sacred Heart, Rome, Italy. dgniuli@hotmail.com
authors.forename: Donatella
authors.initials: D
authors.lastname: Gniuli
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Rosa
authors.forename: Melania
authors.initials: M
authors.lastname: Manco
authors.forename: Antonino
authors.initials: A
authors.lastname: Scarfone
authors.forename: Nathalie
authors.initials: N
authors.lastname: Vega
authors.forename: Aldo V
authors.initials: AV
authors.lastname: Greco
authors.forename: Marco
authors.initials: M
authors.lastname: Castagneto
authors.forename: Hubert
authors.initials: H
authors.lastname: Vidal
authors.forename: Geltrude
authors.initials: G
authors.lastname: Mingrone
mesh_terms: D000273:Adipose Tissue / Q000737:chemistry / Q000378:metabolism*; D015904:Biliopancreatic Diversion; D001823:Body Composition / Q000235:genetics*; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005230:Fatty Acids, Nonesterified / Q000032:analysis; D005260:Female; D015870:Gene Expression; D006006:Glycogen Synthase / Q000235:genetics; D006593:Hexokinase / Q000235:genetics; D006801:Humans; D007333:Insulin Resistance; D007473:Ion Channels; D015227:Lipid Peroxidation; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics*; D018482:Muscle, Skeletal / Q000737:chemistry; D009765:Obesity / Q000235:genetics* / Q000601:surgery; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors / Q000235:genetics*; D000071246:Uncoupling Protein 2
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D005230:Fatty Acids, Nonesterified; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2; D006006:Glycogen Synthase; D006593:Hexokinase