Novel Role of Endogenous Catalase in Macrophage Polarization in Adipose Tissue.
Macrophages are important components of adipose tissue inflammation, which results in metabolic diseases such as insulin resistance. Notably, obesity induces a proinflammatory phenotypic switch in adipose tissue macrophages, and oxidative stress facilitates this switch. Thus, we examined the role of endogenous catalase, a key regulator of oxidative stress, in the activity of adipose tissue macrophages in obese mice. Catalase knockout (CKO) exacerbated insulin resistance, amplified oxidative stress, and accelerated macrophage infiltration into epididymal white adipose tissue in mice on normal or high-fat diet. Interestingly, catalase deficiency also enhanced classical macrophage activation (M1) and inflammation but suppressed alternative activation (M2) regardless of diet. Similarly, pharmacological inhibition of catalase activity using 3-aminotriazole induced the same phenotypic switch and inflammatory response in RAW264.7 macrophages. Finally, the same phenotypic switch and inflammatory responses were observed in primary bone marrow-derived macrophages from CKO mice. Taken together, the data indicate that endogenous catalase regulates the polarization of adipose tissue macrophages and thereby inhibits inflammation and insulin resistance.
Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 120-750, Republic of Korea.
Ye Seul
0000-0001-6718-5482
YS
Park
Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 120-750, Republic of Korea.
Md Jamal
0000-0003-2911-3255
MJ
Uddin
Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 120-750, Republic of Korea.
Lingjuan
0000-0002-3781-875X
L
Piao
Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 120-750, Republic of Korea.
Inah
0000-0002-4479-9374
I
Hwang
Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 120-750, Republic of Korea.
Jung Hwa
0000-0003-1423-3895
JH
Lee
Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 120-750, Republic of Korea.
Hunjoo
0000-0002-5601-1265
H
Ha
D000273:Adipose Tissue / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D007150:Immunohistochemistry; D007333:Insulin Resistance; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction
D002374:Catalase; D000640:Amitrole