Cathepsins in human obesity: changes in energy balance predominantly affect cathepsin s in adipose tissue and in circulation.
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.
Naour
Nadia
N
Institut National de la Santé et de la Recherche Méédicale, Unité 872, Université Pierre et Marie Curie-Paris6, Paris, France.
Rouault
Christine
C
Fellahi
Soraya
S
Lavoie
Marie-Eve
ME
Poitou
Christine
C
Keophiphath
Mayoura
M
Eberlé
Delphine
D
Shoelson
Steve
S
Rizkalla
Salwa
S
Bastard
Jean-Philippe
JP
Rabasa-Lhoret
Rémi
R
Clément
Karine
K
Guerre-Millo
Michèle
M
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
D055316:Cystatin C; D020738:Leptin; D012333:RNA, Messenger; D012313:RNA; D002403:Cathepsins; C028217:cathepsin S