High fat diet induces formation of spontaneous liposarcoma in mouse adipose tissue with overexpression of interleukin 22

• Published in: PloS one 2011-08, Vol.6 (8), p.e23737-e23737
• Main Authors: Wang, Zheng, Yang, Ling, Jiang, Yuhui, Ling, Zhi-Qiang, Li, Zhigang, Cheng, Yuan, Huang, Heng, Wang, Lingdi, Pan, Yi, Wang, Zhenzhen, Yan, Xiaoqiang, Chen, Yan
• Format: Article
• Language: English
• Subjects: Adipocytes; Adipocytes - metabolism; Adipose tissue; Adipose Tissue - metabolism; Analysis; Animal tissues; Animals; Apoptosis; Biology; Body fat; Cancer; Cell cycle; Cell growth; Crohn's disease; Crohns disease; Cytogenetics; Cytokines; Cytokines - biosynthesis; Deoxyribonucleic acid; Diet; Diet, High-Fat - adverse effects; DNA; Epithelium; Extracellular Signal-Regulated MAP Kinases - metabolism; Gene Expression; Genetic engineering; Growth factors; Hepatitis; High fat diet; Infiltration; Inflammation; Inflammatory response; Insulin; Insulin resistance; Interleukin 10; Interleukin 22; Interleukins; Interleukins - genetics; Kinases; Laboratories; Liposarcoma; Liposarcoma - etiology; Liposarcoma - genetics; Liposarcoma - metabolism; Liposarcoma - pathology; Liver; Lymphocytes; Lymphocytes T; Male; Medicine; Melanoma; Metabolism; Metastases; Metastasis; Mice; Mice, Transgenic; Nutrition; Obesity; Phosphorylation; Phosphorylation - genetics; Protein expression; Proteins; T cells; Tissue analysis; Transgenic animals; Transgenic mice; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0023737

Interleukin 22 (IL-22) is a T-cell secreted cytokine that modulates inflammatory response in nonhematopoietic tissues such as epithelium and liver. The function of IL-22 in adipose tissue is currently unknown. We generated a transgenic mouse model with overexpression of IL-22 specifically in adipose tissue. The IL-22 transgenic mice had no apparent changes in obesity and insulin resistance after feeding with high fat diet (HFD). Unexpectedly, all the IL-22 transgenic mice fed with HFD for four months developed spontaneous tumors in epididymal adipose tissue. Histological analysis indicated that the tumors were well-differentiated liposarcomas with infiltration of inflammatory cells. IL-22 overexpression promotes production of inflammatory cytokines such as IL-1β and IL-10 and stimulates ERK phosphorylation in adipose tissue. Furthermore, IL-22 treatment in differentiated 3T3-L1 adipocytes could induce IL-1β and IL-10 expression, together with stimulation of ERK phosphorylation. Taken together, our study not only established a novel mouse model with spontaneous liposarcoma, but also revealed that IL-22 overexpression may collaborate with diet-induced obesity to impact on tumor development in mouse.