Female heterozygous (+/fa) Zucker rats as a novel leptin-related mammary carcinogenesis model

J Toxicol Sci. 2012;37(5):1025-34. doi: 10.2131/jts.37.1025.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Body Weight
  • Corn Oil
  • Diet
  • Disease Models, Animal*
  • Female
  • Leptin / metabolism*
  • Liver / growth & development
  • Mammary Neoplasms, Animal / metabolism*
  • Obesity / metabolism
  • Organ Size
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Zucker
  • Tumor Necrosis Factor-alpha / genetics*
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • Leptin
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat
  • Corn Oil