title: Cathepsins in human obesity: changes in energy balance predominantly affect cathepsin s in adipose tissue and in circulation.
abstract: BACKGROUND
  Recent studies in humans and mice suggest the implication of the cysteine proteases cathepsins S, L, and K in vascular and metabolic complications of obesity.
  
  
  OBJECTIVE
  Our objective was to identify clinically relevant forms of cathepsin in human obesity.
  
  
  METHODS
  We conducted a prospective study on two independent cohorts.
  
  
  METHODS
  The first cohort includes 45 obese women eligible for gastric surgery (age, 39 +/- 1.6 yr; body mass index, 47 +/- 0.99 kg/m(2)) and 17 nonobese women (age, 38 +/- 1.8 yr; body mass index, 21 +/- 0.44 kg/m(2)). The second cohort comprises 29 obese women (age, 57 +/- 0.8 yr; body mass index, 34 +/- 0.69 kg/m(2)) undergoing 6 months of medically supervised caloric restriction.
  
  
  RESULTS
  Cathepsin S, L, and K mRNA levels were determined in surgical adipose tissue biopsies. The proteins were measured in conditioned medium of adipose tissue explants and in circulation.
  
  
  RESULTS
  Obese subjects had a 2-fold increase in cathepsin S mRNA in adipose tissue as compared with normal-weight subjects and an increased rate (1.5-fold) of cathepsin S release in adipose tissue explants. Cathepsin S circulating concentrations were increased with obesity (+30%) and reduced after weight reduction (P < 0.05 for both). By contrast, cathepsin L was unaffected in adipose tissue and serum; cathepsin K was undetectable in circulation and unchanged in adipose tissue.
  
  
  CONCLUSIONS
  In humans, cathepsin S is more influenced than cathepsins L and K by changes in energy balance in adipose tissue and circulation. This opens new avenues to explore whether selective inhibition of this protease could reduce cardiovascular risk and ameliorate metabolic status in obese subjects.
authors.affiliation: Institut National de la Santé et de la Recherche Méédicale, Unité 872, Université Pierre et Marie Curie-Paris6, Paris, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Naour
authors.forename: Christine
authors.initials: C
authors.lastname: Rouault
authors.forename: Soraya
authors.initials: S
authors.lastname: Fellahi
authors.forename: Marie-Eve
authors.initials: ME
authors.lastname: Lavoie
authors.forename: Christine
authors.initials: C
authors.lastname: Poitou
authors.forename: Mayoura
authors.initials: M
authors.lastname: Keophiphath
authors.forename: Delphine
authors.initials: D
authors.lastname: Eberlé
authors.forename: Steve
authors.initials: S
authors.lastname: Shoelson
authors.forename: Salwa
authors.initials: S
authors.lastname: Rizkalla
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Bastard
authors.forename: Rémi
authors.initials: R
authors.lastname: Rabasa-Lhoret
authors.forename: Karine
authors.initials: K
authors.lastname: Clément
authors.forename: Michèle
authors.initials: M
authors.lastname: Guerre-Millo
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000713:Anastomosis, Roux-en-Y; D000818:Animals; D015992:Body Mass Index; D031204:Caloric Restriction; D002403:Cathepsins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D015331:Cohort Studies; D055316:Cystatin C / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D020738:Leptin / Q000097:blood; D051379:Mice; D008820:Mice, Obese; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000378:metabolism*; D017698:Postmenopause / Q000378:metabolism; D011792:Quebec; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015431:Weight Loss
chemical_list: D055316:Cystatin C; D020738:Leptin; D012333:RNA, Messenger; D012313:RNA; D002403:Cathepsins; C028217:cathepsin S