A new genetically obese-hyperglycemic rat (Wistar fatty)

Area of Science:

• Genetics and Physiology
• Metabolic Disease Research

Background:

• The fa-gene, responsible for obesity in Zucker rats, was transferred to Wistar Kyoto (WKY) rats.
• This created a congenic strain, Wistar fatty rats (fa/fa), to study obesity and related conditions.

Purpose of the Study:

• To investigate the development of obesity and related metabolic disorders in the WKY congenic strain.
• To determine the impact of the fa-gene on WKY rat physiology, particularly concerning diabetes.

Main Methods:

• Transfer of the fa-gene from Zucker rats to WKY rats through 10 generations of backcrossing.
• Phenotypic analysis of Wistar fatty rats (fa/fa) for obesity, hyperinsulinemia, hyperlipemia, hyperglycemia, glucosuria, and polyuria.
• Assessment of glucose tolerance and insulin response in male rats of advancing age.
• Comparison of insulin sensitivity between WKY and Zucker rats using glucose tolerance tests and steady-state blood glucose methods.

Main Results:

• Wistar fatty rats (fa/fa) exhibited obesity and related features (hyperinsulinemia, hyperlipemia) comparable to Zucker fatty rats.
• Male Wistar fatty rats, but not females, developed hyperglycemia, glucosuria, and polyuria by 8 weeks of age.
• Decreased glucose tolerance and insulin response were observed in aging male rats.
• WKY rats demonstrated lower insulin sensitivity than Zucker rats, suggesting a predisposition to diabetes.

Conclusions:

• The Wistar fatty rat (fa/fa) serves as a valuable congenic model for studying obesity and associated metabolic diseases.
• Diabetic changes in this model result from an interaction between the inherent insulin resistance of WKY rats and fa-gene-induced obesity.
• The findings highlight the complex interplay between genetic background and specific gene effects in the development of metabolic syndrome.