title: Lipoprotein subclass profiles of hyperlipidemic diabetic mice measured by nuclear magnetic resonance spectroscopy.
abstract: Dyslipidemia accelerates vascular complications of diabetes. Nuclear magnetic resonance (NMR) analysis of lipoprotein subclasses is used to evaluate a mouse model of human familial hypercholesterolemia +/- streptozotocin (STZ)-induced diabetes. A double knockout (DKO) mouse (low-density lipoprotein receptor [LDLr] -/-; apolipoprotein B [apoB] mRNA editing catalytic polypeptide-1 [Apobec1] -/-) was studied. Wild-type (WT) and DKO mice received sham or STZ injections at age 7 weeks, yielding control (WT-C, DKO-C) and diabetic (WT-D, DKO-D) groups. Fasting serum was collected when the mice were killed (age 40 weeks) for Cholestech analysis (Cholestech Corp, Hayward, CA) and NMR lipoprotein subclass profile. By Cholestech, fasting triglyceride and total cholesterol increased in DKO-C versus WT-C. Diabetes further increased total cholesterol in DKO. High-density lipoprotein cholesterol (HDL-C) was similar among all groups. NMR revealed that LDL in all groups was present in a subclass the size of large human LDL and was increased 48-fold in DKO-C versus WT-C animals, but was unaffected by diabetes. HDL was found in a subclass equivalent to large human HDL, and was similar among groups. In conclusion, NMR analysis reveals lipoprotein subclass distributions and the effects of genetic modification and diabetes in mice, but lack of particles the size of human small LDL and small HDL may limit the relevance of the present animal model to human disease.
authors.affiliation: Division of Endocrinology Diabetes and Medical Genetics, Medical University of South Carolina, Charleston 29425, USA.
authors.forename: Samar M
authors.initials: SM
authors.lastname: Hammad
authors.forename: Lyn
authors.initials: L
authors.lastname: Powell-Braxton
authors.forename: James D
authors.initials: JD
authors.lastname: Otvos
authors.forename: Leslie
authors.initials: L
authors.lastname: Eldridge
authors.forename: Wesley
authors.initials: W
authors.lastname: Won
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Lyons
mesh_terms: D000071479:APOBEC-1 Deaminase; D000818:Animals; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D003564:Cytidine Deaminase / Q000172:deficiency / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D004195:Disease Models, Animal; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood* / Q000235:genetics; D008074:Lipoproteins / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010316:Particle Size; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics
chemical_list: D008076:Cholesterol, HDL; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D002784:Cholesterol; D000071479:APOBEC-1 Deaminase; C000605089:APOBEC1 protein, human; C000605090:Apobec1 protein, mouse; D003564:Cytidine Deaminase