title: Amelioration of hypertriglyceridemia with hypo-alpha-cholesterolemia in LPL deficient mice by hematopoietic cell-derived LPL.
abstract: BACKGROUND
  Macrophage-derived lipoprotein lipase (LPL) has been shown uniformly to promote atherosclerotic lesion formation while the extent to which it affects plasma lipid and lipoprotein levels varies in wild-type and hypercholesterolemic mice. It is known that high levels of LPL in the bulk of adipose tissue and skeletal muscle would certainly mask the contribution of macrophage LPL to metabolism of plasma lipoprotein. Therefore, we chose LPL deficient (LPL⁻/⁻) mice with severe hypertriglyceridemia as an alternative model to assess the role of macrophage LPL in plasma lipoprotein metabolism via bone marrow transplant, through which LPL will be produced mainly by hematopoietic cell-derived macrophages.
  
  
  RESULTS
  Hypertriglyceridemic LPL⁻/⁻ mice were lethally irradiated, then transplanted with bone marrow from wild-type (LPL⁺/⁺) or LPL⁻/⁻ mice, respectively. Sixteen weeks later, LPL⁺/⁺ →LPL⁻/⁻ mice displayed significant reduction in plasma levels of triglyceride and cholesterol (408±44.9 vs. 2.7±0.5×10³ and 82.9±7.1 vs. 229.1±30.6 mg/dl, p<0.05, respectively), while a 2.7-fold increase in plasma high density lipoprotein- cholesterol (p<0.01) was observed, compared with LPL⁻/⁻→LPL⁻/⁻ control mice. The clearance rate for the oral fat load test in LPL⁺/⁺ →LPL⁻/⁻ mice was faster than that in LPL⁻/⁻→LPL⁻/⁻ mice, but slower than that in wild-type mice. Liver triglyceride content in LPL⁺/⁺→LPL⁻/⁻ mice was also significantly increased, compared with LPL⁻/⁻→LPL⁻/⁻ mice (6.8±0.7 vs. 4.6±0.5 mg/g wet tissue, p<0.05, n = 6). However, no significant change was observed in the expression levels of genes involved in hepatic lipid metabolism between the two groups.
  
  
  CONCLUSIONS
  Hematopoietic cell-derived LPL could efficiently ameliorate severe hypertriglyceridemia and hypo-alpha-cholesterolemia at the compensation of increased triglyceride content of liver in LPL⁻/⁻ mice.
authors: Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Peking University, Beijing, China.
authors: Yinyuan
authors: Y
authors: Ding
authors: Ling
authors: L
authors: Zhang
authors: Yuhui
authors: Y
authors: Wang
authors: Wei
authors: W
authors: Huang
authors: Yin
authors: Y
authors: Tang
authors: Lu
authors: L
authors: Bai
authors: Colin J D
authors: CJ
authors: Ross
authors: Michael R
authors: MR
authors: Hayden
authors: George
authors: G
authors: Liu
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D002784:Cholesterol / Q000097:blood*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006410:Hematopoiesis; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood* / Q000201:enzymology* / Q000378:metabolism / Q000601:surgery; D008071:Lipoprotein Lipase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D008074:Lipoproteins / Q000097:blood; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000166:cytology / Q000201:enzymology; D051379:Mice; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
chemical_list: D008074:Lipoproteins; D014280:Triglycerides; D002784:Cholesterol; D008071:Lipoprotein Lipase