Is this diet very crumbly - is there some food mixes with consistency that I should avoid? I need mice that develop fasting hyperglycemia. Should I use a mixed protocol of DIO and STZ?
We generally use a 60%, lard-based high fat diet. Because of the large amount of fat it holds together well. After 8 weeks on this diet our mice typically develop hyperglycemia and hyperinsulinemia. We purchase our diet from Research Diets (D12492).
I agree with Cory. rmoreover, this diet can be suppelmented with N-3 Fatty Acids and other long chain polyansurated Fatty acids. If you want a chylomicron -enriched diet you can use Intralipid instead of the above mentioned diets. Remember that Mice lack Cholesterol Ester Transfer Protein (CETP). The election of fat enriched diet depends on the objective of your Project.
Also remember that the hyperglycemic responses are highly dependent of the choice of mice strain. Such high fat diet are quite soft and if you plan to give the mice such a high fat diet over several weeks, you probably also should consider giving the mice wooden sticks (or similar) for maintaining proper teeth length and normal diet intake.
If you want the mice to develop full on Diabetes then yes DIO and STZ will ensure you get full Pancreatic Failure. Rodents are very resistant to diabetes due to DIO. Regarding fasting Hyperglycemia then length of time you fast them for (overnight versus 6hours) will alter the glucose levels you see.
An example of a High Fat diet in order to induce obesity and Insulin Resistance IR) resulting in type 2 diabetes after 6 weeks is given below. The high fat diet based on bovine lard gave us afterwards in a C57BL6 mouse model in all non-adipose tissue two interesting biomarkers (patented).
Afterwards -using LCMS lipidomics techniques based on a Systems Biology approach- we would chose for another experimental set up and eliminate the Cholesterol compound because we couldn't for the measured parameters not directly gave convincing evidence what was the "preliminary cause" for several parameters in the pathogenesis of the obesity=>IR=>DM2: bovine lard or Cholesterol. I hope this information might be helpfull in developing your experimental set up. Success Dr.Dr.Ir.Vincent van Ginneken, Chairman and Scientific Director of the Bluegreentechnologies foundation (see:] Ginneken, V.J.T. van; Verheij, E.; Hekman, M.; Greef, J. van der; Feskens, E.J.M.; Poelmann, R.E. (2011). The comparison of lipid profiling in mouse brain and liver after starvation and a high-fat diet. A medical systems biology approach. In: Biology of Starvation in Humans and Other Organisms. Chapter 3 (pp. 151-186): Editor: Todd C. Merkin Nova Science Publishers Inc.; ISBN: 978-1-61122-546-4. Please can you endorse me on LinkedIn, our foundation needs some endorsements. Thanks all the best Vincent
Make sure you match micronutrients of your low fat (control) diet to your high fat diet. In the past Research Diets standard diets did not have this controlled and one of the diets had to be custom matched to the other. Regular lab chow is not an appropriate control .
I agree with most of the comments above. Each type of dietary fat elicit different effects. To induce hypercholesterolemia,other factors(i.e.: cholic acid) shall be included in the diet. Also different strains respond differently to the same dietary fats. Remember, that (not transgenic) rodents are quite resistant to develop fat deposition in vessel wall. Very important, it will be your control group that shall have the same type of energy intake, because each dietary variation induce different energy intake.
Thanks for the answers. One thing I learned in the meantime was that a transition from grain to specified contents diet to HFD seems important. I like the answer regarding wooden sticks, since this is sth. we sometimes do with normal chow but sth. I would have never considered before seeing sth. is wrong! The micronutrients I'll keep in mind for the future, right now I'm comparing WT/KO mice, all on HFD, without control diet.