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Regulation of cathepsins in adipose tissue and macrophages in obesity
Author(s) -
Hannaford Jennifer Elyse,
Chen Xiaoli
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.547.6
Subject(s) - cathepsin , adipose tissue , endocrinology , medicine , cathepsin s , inflammation , adipose tissue macrophages , cathepsin b , cathepsin k , chemistry , biology , white adipose tissue , biochemistry , receptor , enzyme , osteoclast
Obesity and its related chronic inflammation are major risk factors for developing metabolic disturbances. The roles of cathepsins, cysteine proteases, have been tied to adipogenesis, inflammation, and atherosclerosis. The objectives of this study were to examine the regulation of cathepsins in adipose tissue and macrophages in genetic and diet‐induced obesity, and explore cathepsin activity with cholesterol metabolism macrophages. We found cathepsins to be upregulated in obese Zucker rats compared to lean counterparts, especially in the stromal vascular (S‐V) fraction of adipose tissue. Mice fed high fat diet compared to low fat diet showed increased cathepsin protein expression in adipose tissue; this affect was attenuated with a PPARγ agonist. TNFα did not affect cathepsin L expression in 3T3‐L1 adipocytes, but LPS simulation significantly increased cathepsin L expression in Raw264.7 macrophages. This supported in vivo data that the S‐V fraction accounted for increased cathepsin expression in obesity. In regards to cholesterol metabolism, LPS inflammatory stimulation of macrophages lead to an increased expression of NPC2, a cholesterol trafficking protein; NPC2 expression was decreased with cathepsin inhibitors in basal and LPS‐stimulated states in macrophages. In conclusion, cathepsins appear to be involved in the inflammatory response and in cholesterol metabolism. Grant Funding Source : National Institute of Diabetes and Digestive and Kidney Diseases Grant No. 2 P30DK050456 (Minnesota Obesity Center)