title: Female heterozygous (+/fa) Zucker rats as a novel leptin-related mammary carcinogenesis model.
abstract: The homozygous mutant fatty Zucker rat (fa/fa) is the prominent model for the research of obesity, one of the most well-known risk factor of postmenopausal mammary cancer. But the usage as a mammary gland carcinogenesis model is considered to be restricted due to the hypoplasia of mammary gland. In the present study, to find the validity of heterozygous mutant (+/fa) lean Zucker rats as a new leptin-related mammary carcinogenesis model, we examined whether the number of terminal end buds of mammary gland, the serum biochemistry, leptin concentration in serum and adipose tissue are changed in 7-week-old female +/+, +/fa and fa/fa rats, and whether these changes and leptin, TNF-α and VEGF mRNA expression in adipose tissue of +/+ and +/fa rats are influenced by 10% corn oil diet for 5 weeks. We confirmed that mild hyperleptinemia was more pronounced in 7-week-old +/fa as compared with wild type (+/+) and hypoplasia of mammary glands characterized by fewer numbers of terminal end buds in fa/fa was not observed in +/fa. With 10% corn oil diet, leptin mRNA expression in adipose tissue showed increasing tendency both in +/fa and +/+. Comparing with +/+, adipose tissue in +/fa treated with 10% corn oil diet was found to be significantly increased in the concentration of leptin protein and tended to be elevated expression of TNF-α mRNA. These results suggest that +/fa with 10% corn oil diet may be a useful model for investigation of the participation of leptin and TNF-α in mammary gland carcinogenesis.
authors.affiliation: Division of Pathology, National Institute of Health Sciences, Setagaya-Ku, Tokyo, Japan. ymcho@nihs.go.jp
authors.forename: Young-Man
authors.initials: YM
authors.lastname: Cho
authors.forename: Toshio
authors.initials: T
authors.lastname: Imai
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Takami
authors.forename: Kumiko
authors.initials: K
authors.lastname: Ogawa
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Nishikawa
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D003314:Corn Oil; D004032:Diet; D004195:Disease Models, Animal; D005260:Female; D020738:Leptin / Q000378:metabolism*; D008099:Liver / Q000254:growth & development; D015674:Mammary Neoplasms, Animal / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D009929:Organ Size; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D020738:Leptin; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D003314:Corn Oil