title: Extensive metabolic disorders are present in APC(min) tumorigenesis mice.
abstract: 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.
authors.affiliation: Cardiovascular Division, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Cardiovascular Division, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Cardiovascular Division, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Zhengxiang
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Cardiovascular Division, Xiangya Hospital, Central South University, Changsha, China; Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Mao
authors.affiliation: Department of Histology and Embryology, Xiangya School of Medicine, Central South University, Changsha, China.
authors.forename: Jinxing
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Histology and Embryology, Xiangya School of Medicine, Central South University, Changsha, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Xiong
authors.affiliation: Department of Histology and Embryology, Xiangya School of Medicine, Central South University, Changsha, China.
authors.forename: Chaonan
authors.initials: C
authors.lastname: Liao
authors.affiliation: Department of Anatomy and Neuroscience, Xiangya School of Medicine, Central South University, Changsha, China.
authors.forename: Fulian
authors.initials: F
authors.lastname: Huang
authors.affiliation: Endocrinology Division, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Zehao
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Cardiovascular Division, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Md Sayed
authors.initials: MS
authors.lastname: Ali Sheikh
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Jorge
authors.initials: J
authors.lastname: Plutzky
authors.affiliation: Department of Histology and Embryology, Xiangya School of Medicine, Central South University, Changsha, China. Electronic address: huanghe@csu.edu.cn.
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.affiliation: Cardiovascular Division, Xiangya Hospital, Central South University, Changsha, China. Electronic address: tianluny@163.com.
authors.forename: Tianlun
authors.initials: T
authors.lastname: Yang
authors.affiliation: Cardiovascular Division, Xiangya Hospital, Central South University, Changsha, China. Electronic address: qiongorwu@163.com.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Duan
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000097:blood / Q000150:complications* / Q000235:genetics; D050156:Adipogenesis; D000818:Animals; D001833:Body Temperature Regulation; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D008055:Lipids / Q000097:blood; D008297:Male; D008659:Metabolic Diseases / Q000097:blood / Q000209:etiology*; D051379:Mice; D015431:Weight Loss
chemical_list: D005227:Fatty Acids; D008055:Lipids
keywords: APC(min) mice; Adipogenesis; Hyperglycemia; Thermogenesis