title: A role of apolipoprotein D in triglyceride metabolism.
abstract: Apolipoproteins (apo) are constituents of lipoproteins crucial for lipid homeostasis. Aberrant expression of apolipoproteins is associated with metabolic abnormalities. Here we characterized apolipoprotein D (apoD) in triglyceride metabolism. Unlike canonical apolipoproteins that are mainly produced in the liver, apoD is an atypical apolipoprotein with broad tissue distribution. We show that circulating apoD is present mainly in HDL and, to a lesser extent, in LDL and VLDL and that its plasma levels were reduced in db/db mice with visceral obesity and altered lipid metabolism. Elevated apoD production, derived from adenovirus-mediated gene transfer, resulted in significant reduction in plasma triglyceride levels in mice. This effect was attributable to en-hanced LPL activity and improved catabolism of triglyceride-rich particles. In contrast, VLDL triglyceride production remained unchanged in response to elevated apoD production. These findings were recapitulated in high-fat-induced obese mice. Obese mice with elevated apoD production exhibited significantly improved triglyceride profiles, correlating with increased plasma LPL activity and enhanced postprandial fat tolerance. ApoD was shown to promote LPL-mediated hydrolysis of VLDL in vitro, correlating with its TG-lowering action in vivo. Apolipoprotein D plays a significant role in lipid metabolism. These data provide important clues to clinical observations that genetic variants of apoD are associated with abnormal lipid metabolism and increased risk of metabolic syndrome.
authors.affiliation: Rangos Research Center, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: German
authors.initials: G
authors.lastname: Perdomo
authors.forename: Dae Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Shen
authors.initials: S
authors.lastname: Qu
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Thomas
authors.forename: Frederico G S
authors.initials: FG
authors.lastname: Toledo
authors.forename: Sandra
authors.initials: S
authors.lastname: Slusher
authors.forename: Yong
authors.initials: Y
authors.lastname: Fan
authors.forename: David E
authors.initials: DE
authors.lastname: Kelley
authors.forename: H Henry
authors.initials: HH
authors.lastname: Dong
mesh_terms: D000818:Animals; D053399:Apolipoproteins D / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D002417:Cattle; D015971:Gene Expression Regulation, Enzymologic; D008071:Lipoprotein Lipase / Q000097:blood / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D009765:Obesity / Q000097:blood / Q000378:metabolism; D014280:Triglycerides / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*
chemical_list: D053399:Apolipoproteins D; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D008071:Lipoprotein Lipase