Diabetic Genetics and Diet Manipulation in ZDF Rats

Many disease-specific rat models are quite sensitive to diet manipulation. Such sensitivity appears particularly prevalent in those rats that have diabetic genetics.

Diets for the ZDF (Zucker Diabetic Fatty) Rat

The ZDF is an inbred rat model that, through genetic mutation and a managed diet, will closely mimic human adult onset diabetes (Type 2) and related complications.

Male    When fed a diet of Purina LabDiet^® 5008 homozygous recessive ZDF males (fa/fa) develop obesity, hyperlipidemia, fasting hyperglycemia, and Type 2 diabetes (NIDDM).  Homozygous dominant (+/+) and heterozygous (fa/+) lean genotypes remain normoglycemic.

Purina LabDiet^® 5008 has a guaranteed analysis (by weight) as follows:

Protein                  not less than 23.0%

Fat                        not less than   6.5%

Fiber                      not more than  4.0%

Ash                       not more than  8.0%

Added Minerals      not more than  2.5%

Complete specifications can be found at www.LabDiet.com/pdf/5008.pdf

Female    The obese female ZDF rat does not typically develop diabetes on Purina LabDiet^® 5008 or other commercially available rodent diets.  However, these rats consistently become diabetic within approximately one month when fed Purina TestDiet^® 58NX.  Diabetes in the female can be initiated after 6 weeks and up to 25 weeks of age.  The obese female ZDF fed the Purina TestDiet^® 58NXdiet has a slower beta cell depletion rate than that of the male (fed LabDiet 5008) which preserves blood insulin levels for a longer period of time.  The prolonged onset of diabetes allows for extended study of the development of diabetes and the effects of anti-diabetic drugs.  Additionally, the obese female diabetic ZDF is hypertensive; the non-diabetic ZDF obese female is normotensive.

Diabetogenic Purina TestDiet^® 58NX

The Purina TestDiet^® 58NX formula has also been known as “Gmi/RD13004” and “C13004.”  This diet was developed by Genetic Models Incorporated (GMI) and evaluated specifically to create a female rat model that would express NIDDM (non-insulin dependent diabetes mellitus).*  Based on Purina LabDiet^® 5015, Purina TestDiet^® 58NX also contains a concentrated fat source and supplemental carbohydrate.  When fed this diet, inbred ZDF female and ZSF1 hybrid female rats become diabetic.  Purina TestDiet^® 58NX also prompts and/or accelerates NIDDM in hybrid males that have ZDF genetics.  Studies found that the different diets produced significantly different physiological and histological effects.  This variance in expression is a result of differences in the macro constituent and component formulations of the diets. 

*The ZDF models were transferred to Charles River Labs (CRL) when CRL acquired GMI.