Hyperlipidemia is a major risk factor in the development of atherosclerosis, but the molecules that control plasma lipid levels remain unknown. In January 14 online Nature Genetics, Ryuta Koishi and colleagues from Sankyo Company, Tokyo, Japan show that angiopoietin-like protein 3 — encoded by Angptl3 — regulates lipid metabolism in mice.

Using a murine model of obesity Koishi et al. identified a hypolipidemia (hypl) locus in the middle of chromosome 4 that encodes a unique angiopoietin-like lipoprotein modulator. This modulator was named Allm1 and proved to be identical to angiopoietin-like protein 3, encoded by Angptl3. Overexpression of Angptl3 or intravenous injection of the purified protein in these mice elicited an increase in circulating plasma lipid levels (Nat Genet 2002, DOI:10.1038/ng814).

Because Angptl3 (and its human ortholog) is secreted "Angptl3 may be a useful target in the development of new treatments of atherosclerosis and...

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