The Role of SHIP1 on Apoptosis and Autophagy in the Adipose Tissue of Obese Mice

• Main Authors: Jae Hun Jeong, Eun Bee Choi, Hye Min Jang, Yu Jeong Ahn, Hyeong Seok An, Jong Youl Lee, Gyeongah Park, Eun Ae Jeong, Hyun Joo Shin, Jaewoong Lee, Kyung Eun Kim, Gu Seob Roh
• Format: Article
• Language: English
• Published: MDPI AG 2020-09-01
• Series: International Journal of Molecular Sciences
• Subjects: SHIP1; macrophage; apoptosis; autophagy; adipose tissue; obesity
• Online Access: https://www.mdpi.com/1422-0067/21/19/7225

Obesity-induced adipocyte apoptosis promotes inflammation and insulin resistance. Src homology domain-containing inositol 5′-phosphatase 1 (SHIP1) is a key factor of apoptosis and inflammation. However, the role of SHIP1 in obesity-induced adipocyte apoptosis and autophagy is unclear. We found that diet-induced obesity (DIO) mice have significantly greater crown-like structures and terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL)-positive cells than ob/ob or control mice. Using RNA sequencing (RNA-seq) analysis, we identified that the apoptosis- and inflammation-related gene Ship1 is upregulated in DIO and ob/ob mice compared with control mice. In particular, DIO mice had more SHIP1-positive macrophages and lysosomal-associated membrane protein 1 (LAMP1) as well as a higher B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax)/Bcl-2 ratio compared with ob/ob or control mice. Furthermore, caloric restriction attenuated adipose tissue inflammation, apoptosis, and autophagy by reversing increases in SHIP1-associated macrophages, Bax/Bcl2-ratio, and autophagy in DIO and ob/ob mice. These results demonstrate that DIO, not ob/ob, aggravates adipocyte inflammation, apoptosis, and autophagy due to differential SHIP1 expression. The evidence of decreased SHIP1-mediated inflammation, apoptosis, and autophagy indicates new therapeutic approaches for obesity-induced chronic inflammatory diseases.