RRC ID 67777
Author Mizunoe Y, Kobayashi M, Hoshino S, Tagawa R, Itagawa R, Hoshino A, Okita N, Sudo Y, Nakagawa Y, Shimano H, Higami Y.
Title Cathepsin B overexpression induces degradation of perilipin 1 to cause lipid metabolism dysfunction in adipocytes.
Journal Sci Rep
Abstract Obesity, caused by the dysfunction of white adipose tissue (WAT), is reportedly accompanied by exacerbation of lipolysis. Perilipin 1 (PLIN1), which forms a coat around lipid droplets, interacts with several lipolysis proteins to regulate lipolysis. While it is known that perilipin family proteins are degraded in lysosomes, the underlying molecular mechanisms related to the downregulated expression of PLIN1 in obese WAT remain unknown. Recently, we found that lysosomal dysfunction originating from an abnormality of cathepsin B (CTSB), a lysosomal representative protease, occurs in obese WAT. Therefore, we investigated the effect of CTSB alterations on PLIN1 expression in obese WAT. PLIN1 protein disappeared and CTSB protein appeared in the cytoplasm of adipocytes in the early stage of obese WAT. Overexpression of CTSB reduced PLIN1 protein in 3T3L1 adipocytes, and treatment with a CTSB inhibitor significantly recovered this reduction. In addition, CTSB overexpression induced the dysfunction of lipolysis in 3T3L1 adipocytes. Therefore, we concluded that upregulation of CTSB induced the reduction of PLIN1 protein in obese WAT, resulting in lipolysis dysfunction. This suggests a novel pathology of lipid metabolism involving PLIN1 in adipocytes and that CTSB might be a therapeutic candidate molecule for obese WAT.
Volume 10(1)
Pages 634
Published 2020-1-20
DOI 10.1038/s41598-020-57428-6
PII 10.1038/s41598-020-57428-6
PMID 31959889
PMC PMC6971249
MeSH 3T3 Cells Adipocytes, White / metabolism* Animals Cathepsin B / genetics* Cathepsin B / metabolism* Down-Regulation Gene Expression* Lipid Metabolism / genetics* Lipolysis / genetics Lysosomes / physiology Mice Perilipin-1 / genetics* Perilipin-1 / metabolism*
IF 3.998
DNA material pMXs-AMNN-Puro-mCherry-CTSB (RDB18953)