Extensive metabolic disorders are present in APC(min) tumorigenesis mice
| Autor: | Sayed Ali Sheikh, Jinxing Cai, Zehao Liu, Tianlun Yang, Zhengxiang Zhou, Lu Xiong, Yi Xiao, He Huang, Fulian Huang, Zhenzhen Liu, Xiaoxiao Mao, Jorge Plutzky, Chaonan Liao, Qiong Duan |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Adenomatous polyposis coli Biology Gene mutation Biochemistry Familial adenomatous polyposis 03 medical and health sciences Mice Endocrinology Metabolic Diseases Lipid droplet Internal medicine Weight Loss medicine Animals Molecular Biology Adipogenesis Metabolic disorder Fatty Acids Wnt signaling pathway Lipid metabolism medicine.disease Lipids 030104 developmental biology Adenomatous Polyposis Coli biology.protein Female Body Temperature Regulation |
| Zdroj: | Molecular and cellular endocrinology. 427 |
| ISSN: | 1872-8057 |
| Popis: | Wnt signaling plays essential role in mesenchymal stem cell (MSC) differentiation. Activation of Wnt signaling suppresses adipogenesis, but promotes osteogenesis in MSC. Adenomatous polyposis coli (APC) is a negative regulator of β-catenin and Wnt signaling activity. The mutation of APC gene leads to the activation of Wnt signaling and is responsible for tumorigenesis in APC(min) mouse; however, very few studies focused on its metabolic abnormalities. The present study reports a widespread metabolic disorder phenotype in APC(min) mice. The old APC(min) mice have decreased body weight and impaired adipogenesis, but severe hyperlipidemia, which mimic the phenotypes of Familial Adenomatous Polyposis (FAP), an inherited disease also caused by APC gene mutation in human. We found that the expression of lipid metabolism and free fat acids (FA) use genes in the white adipose tissue (WAT) of the APC(min) mice is much lower than those of control. The changed gene expression pattern may lead to the disability of circulatory lipid transportation and storage at WAT. Moreover, the APC(min) mice could not maintain the core body temperature in cold condition. PET-CT determination revealed that the BAT of APC(min) mice has significantly impaired ability to take up (18)FDG from the blood. Morphological studies identified that the brown adipocytes of APC(min) mice were filled with lipid droplets but fewer mitochondria. These results matched with the findings of impaired BAT function in APC(min) mice. Collectively, our study explores a new mechanism that explains abnormal metabolism in APC(min) mice and provides insights into studying the metabolic disorders of FAP patients. |
| Databáze: | OpenAIRE |
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