Does anyone know if the lipid levels in mice are comparable to humans ? What is the best method to measure LDL/HDL choleterol and TG in mice ? In advance, thank you for your help.
You will find informations on charles rivers website. Choose the strain you want and go to technical resources. here is an exemple for C57Bl/6
http://www.criver.com/files/pdfs/rms/c57bl6/rm_rm_r_c57bl6_mouse_clinical_pathology_data.aspx
It depends of the background of mice that you are using and the metabolic condition of them. Mice have a higher metabolic rate than humans and this affects to levels of NEFA and lipoproteins. I use volumetric assays of wako diagnostics, really easy to use.
Basically amount of circulating lipophorins occurs near about similar, but the net concentration of LDL/HDL choleterol and TG in mice varies from the human. You can use kit for estimation og cholesterol. HPLC coupled to an ELSD detector can isolate the lipoprotein fractions. You can fractionate lipids by a simple method (chloroform/methanol) and can analyse the lipid extract by HPLC. In a single run you can get the major lipid classes (cholesterol esters, TG, cholesterol, diglycerides, monoglycerides and phospholipids)
In rat, for example, lipoproteins metabolism differs compared with human. The LDL represent .5 to 2% of total Lp. The VLDL remnants are found and LDL are associated with HDL1, The HDL2-HDL3 particles are important. The different fractions can be separated by precipitation with MgCl2 and dextran sulphate according to Bustein et al. (1989). All lipids were analysed by kits methods.
Use einher FPLC to separate apoB containing lipoproteins from HDL followed by cholesterol measurement of the fractions (Wako, Roche..commercial kits); or measure total cholesterol and then deplete apoB containing lipoproteins in a test tube followed by cholesterol measurements using commercially available kits (Wako, Roche...).
C57BL/6 mice are the ones mostly used in cholesterol/TG research. However, they cannot be directly compared to humans because they lack CETP, displaying much more HDL than apoB containing lipoproteins. Moreover, B6 mice do not spontaneously develop athero. A good mouse model to be used in cholesterol research would be apoE-/- mice crossed with tgCETP, which have a more man-like lipoprotein profile and develop athero.
Rat and Human have a substantially different lipoprotein circulating pattern profile (have a look , as well, to Cantafora A, Bravo E, Yan CC. Characterization of lipoprotein fractions isolated from plasma of male Wistar rats by gradient ultracentrifugation. PSEBM 1993; 204, 90-96, which include fundamental references in the field) and different metabolism ( apoB48 is secreted both from liver and intestine, for instance). Humans are "LDL animals" and rat are "HDL animal". This imply a different profile after high fat diet, and, it may be supposed that also receptor affinity between the human lipoproteins and the rat tissue may not be perfect
simply sir,
in one study ---No, it is not suitable
but as effection by confounding factors --- yes, it is camparable
In my opinion the lipid profile of human can be compare with rats. Because the anatomy is same as in human hence the factors affecting may be the same as human.
I agree with Elena, Malika, Jose and Ravi: apoB metabolism is completely different in mice/rats compared to humans. Thus, you may use wild-type mice or rats to receive a first guess on whether your compound/diet/therapeutic will influence lipid metabolism. But if you want to better translate it to the human setting, you will have to use CETP-expressing animals with similar apoB-metabolism to humans, which include CETPtg-mice, rabbits, or even hamsters. It may be a matter of how much you will be disposed to spend on research animals, but using CETPtg mice will ease many things: there is a myriad of commercially available antibodies, established and published PCRs etc... for rabbits and hamsters, and even rats you will have to establish many things by your own which is very time-consuming, and in the end again expensive.
But to your first question: to measure total-cholesterol, apoB-depleted cholesterol (=HDL) and TG in mice the easiest way will be to use commercially available kits from Roche, Wako or other companies, UC and FPLC may be a next step.
If you need to differentiate between C, CE, different fatty acids etc, HPLC will be the method of choice.
Human and rats have a substantially different lipoprotein circulating pattern profile , so it might be different.