Cathepsins in human obesity: changes in energy balance predominantly affect cathepsin s in adipose tissue and in circulation.

CONTEXT

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.

DESIGN AND SETTING

We conducted a prospective study on two independent cohorts.

PARTICIPANTS AND INTERVENTIONS

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.

MAIN OUTCOMES

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.

CONCLUSION

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.