Abstract:
:We used gene knockout mice to explore the role of Angiopoietin-like-4 (Angptl4) in lipid metabolism as well as to generate anti-Angptl4 mAbs with pharmacological activity. Angptl4 -/- mice had lower triglyceride (TG) levels resulting both from increased very low-density lipoprotein (VLDL) clearance and decreased VLDL production and had modestly lower cholesterol levels. Also, both Angptl4 -/- suckling mice and adult mice fed a high-fat diet showed reduced viability associated with lipogranulomatous lesions of the intestines and their draining lymphatics and mesenteric lymph nodes. Treating C57BL/6J, ApoE -/-, LDLr -/-, and db/db mice with the anti-Angptl4 mAb 14D12 recapitulated the lipid and histopathologic phenotypes noted in Angptl4 -/- mice. This demonstrates that the knockout phenotype reflects not only the physiologic function of the Angptl4 gene but also predicts the pharmacologic consequences of Angptl4 protein inhibition with a neutralizing antibody in relevant models of human disease.
journal_name
Proc Natl Acad Sci U S Aauthors
Desai U,Lee EC,Chung K,Gao C,Gay J,Key B,Hansen G,Machajewski D,Platt KA,Sands AT,Schneider M,Van Sligtenhorst I,Suwanichkul A,Vogel P,Wilganowski N,Wingert J,Zambrowicz BP,Landes G,Powell DRdoi
10.1073/pnas.0705041104subject
Has Abstractpub_date
2007-07-10 00:00:00pages
11766-71issue
28eissn
0027-8424issn
1091-6490pii
0705041104journal_volume
104pub_type
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