title: Adipose-specific lipoprotein lipase deficiency more profoundly affects brown than white fat biology.
abstract: Adipose fat storage is thought to require uptake of circulating triglyceride (TG)-derived fatty acids via lipoprotein lipase (LpL). To determine how LpL affects the biology of adipose tissue, we created adipose-specific LpL knock-out (ATLO) mice, and we compared them with whole body LpL knock-out mice rescued with muscle LpL expression (MCK/L0) and wild type (WT) mice. ATLO LpL mRNA and activity were reduced, respectively, 75 and 70% in gonadal adipose tissue (GAT), 90 and 80% in subcutaneous tissue, and 84 and 85% in brown adipose tissue (BAT). ATLO mice had increased plasma TG levels associated with reduced chylomicron TG uptake into BAT and lung. ATLO BAT, but not GAT, had altered TG composition. GAT from MCK/L0 was smaller and contained less polyunsaturated fatty acids in TG, although GAT from ATLO was normal unless LpL was overexpressed in muscle. High fat diet feeding led to less adipose in MCK/L0 mice but TG acyl composition in subcutaneous tissue and BAT reverted to that of WT. Therefore, adipocyte LpL in BAT modulates plasma lipoprotein clearance, and the greater metabolic activity of this depot makes its lipid composition more dependent on LpL-mediated uptake. Loss of adipose LpL reduces fat accumulation only if accompanied by greater LpL activity in muscle. These data support the role of LpL as the "gatekeeper" for tissue lipid distribution.
authors.affiliation: Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032.
authors.forename: Itsaso
authors.initials: I
authors.lastname: Garcia-Arcos
authors.affiliation: Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032.
authors.forename: Yaeko
authors.initials: Y
authors.lastname: Hiyama
authors.affiliation: Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Drosatos
authors.affiliation: Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032.
authors.forename: Kalyani G
authors.initials: KG
authors.lastname: Bharadwaj
authors.affiliation: Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032.
authors.forename: Yunying
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032.
authors.forename: Ni Huiping
authors.initials: NH
authors.lastname: Son
authors.affiliation: Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032.
authors.forename: Sheila M
authors.initials: SM
authors.lastname: O'Byrne
authors.affiliation: Institute of Human Nutrition, Columbia University College of Physicians and Surgeons, New York, New York 10032.
authors.forename: Chuchun L
authors.initials: CL
authors.lastname: Chang
authors.affiliation: Institute of Human Nutrition, Columbia University College of Physicians and Surgeons, New York, New York 10032.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Deckelbaum
authors.affiliation: Department of Medicine, Jichii University, Tochigi 329-0498, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032; Department of Medical Biochemistry, University of Amsterdam, 1105AZ Amsterdam, The Netherlands.
authors.forename: Marit
authors.initials: M
authors.lastname: Westerterp
authors.affiliation: Department of Biological Sciences, New York City College of Technology, City University of New York, Brooklyn, New York 11201.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Obunike
authors.affiliation: Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032.
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Medicine, Jichii University, Tochigi 329-0498, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yagyu
authors.affiliation: Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032.
authors.forename: William S
authors.initials: WS
authors.lastname: Blaner
authors.affiliation: Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032. Electronic address: ijg3@columbia.edu.
authors.forename: Ira J
authors.initials: IJ
authors.lastname: Goldberg
mesh_terms: D017667:Adipocytes / Q000166:cytology; D000273:Adipose Tissue / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D016026:Bone Marrow Transplantation; D002914:Chylomicrons / Q000493:pharmacokinetics; D008055:Lipids / Q000737:chemistry; D008066:Lipolysis; D008071:Lipoprotein Lipase / Q000172:deficiency* / Q000235:genetics*; D008264:Macrophages / Q000166:cytology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
chemical_list: D002914:Chylomicrons; D008055:Lipids; D014280:Triglycerides; D008071:Lipoprotein Lipase
keywords: Adipocyte; Fatty Acid; Hypertriglyceridemia; Lipids; Macrophages; Obesity
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