title: Kidney triglyceride accumulation in the fasted mouse is dependent upon serum free fatty acids.
abstract: Lipid accumulation is a pathological feature of every type of kidney injury. Despite this striking histological feature, physiological accumulation of lipids in the kidney is poorly understood. We studied whether the accumulation of lipids in the fasted kidney are derived from lipoproteins or NEFAs. With overnight fasting, kidneys accumulated triglyceride, but had reduced levels of ceramide and glycosphingolipid species. Fasting led to a nearly 5-fold increase in kidney uptake of plasma [14C]oleic acid. Increasing circulating NEFAs using a β adrenergic receptor agonist caused a 15-fold greater accumulation of lipid in the kidney, while mice with reduced NEFAs due to adipose tissue deficiency of adipose triglyceride lipase had reduced triglycerides. Cluster of differentiation (Cd)36mRNA increased 2-fold, and angiopoietin-like 4 (Angptl4), an LPL inhibitor, increased 10-fold. Fasting-induced kidney lipid accumulation was not affected by inhibition of LPL with poloxamer 407 or by use of mice with induced genetic LPL deletion. Despite the increase in CD36 expression with fasting, genetic loss of CD36 did not alter fatty acid uptake or triglyceride accumulation. Our data demonstrate that fasting-induced triglyceride accumulation in the kidney correlates with the plasma concentrations of NEFAs, but is not due to uptake of lipoprotein lipids and does not involve the fatty acid transporter, CD36.
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, New York University School of Medicine, New York, NY.|Institute of Human Nutrition, Columbia University, New York, NY.
authors.forename: Diego
authors.initials: D
authors.lastname: Scerbo
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, New York University School of Medicine, New York, NY.
authors.forename: Ni-Huiping
authors.initials: NH
authors.lastname: Son
authors.affiliation: Department of Cell Biology, State University of New York Downstate Medical Center, Brooklyn, NY.
authors.forename: Alaa
authors.initials: A
authors.lastname: Sirwi
authors.affiliation: Division of Nephrology, University of Michigan, Ann Arbor, MI.
authors.forename: Lixia
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Division of Nephrology, University of Michigan, Ann Arbor, MI.
authors.forename: Kelli M
authors.initials: KM
authors.lastname: Sas
authors.affiliation: Department of Medicine, Washington University, St. Louis, MO.
authors.forename: Vincenza
authors.initials: V
authors.lastname: Cifarelli
authors.affiliation: Division of Endocrinology, University of Pittsburgh, Pittsburgh, PA.|Institute of Molecular Biosciences, University of Graz, Graz, Austria.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Schoiswohl
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, New York University School of Medicine, New York, NY.
authors.forename: Lesley-Ann
authors.initials: LA
authors.lastname: Huggins
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, New York University School of Medicine, New York, NY.
authors.forename: Namrata
authors.initials: N
authors.lastname: Gumaste
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, New York University School of Medicine, New York, NY.
authors.forename: Yunying
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Division of Nephrology, University of Michigan, Ann Arbor, MI.
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Pennathur
authors.affiliation: Department of Medicine, Washington University, St. Louis, MO.
authors.forename: Nada A
authors.initials: NA
authors.lastname: Abumrad
authors.affiliation: Division of Endocrinology, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Kershaw
authors.affiliation: Department of Cell Biology, State University of New York Downstate Medical Center, Brooklyn, NY.
authors.forename: M Mahmood
authors.initials: MM
authors.lastname: Hussain
authors.affiliation: Division of Renal Electrolyte and Hypertension, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Katalin
authors.initials: K
authors.lastname: Susztak
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, New York University School of Medicine, New York, NY ira.goldberg@nyumc.org.
authors.forename: Ira J
authors.initials: IJ
authors.lastname: Goldberg
mesh_terms: D000818:Animals; D005215:Fasting / Q000097:blood* / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D005230:Fatty Acids, Nonesterified; D014280:Triglycerides
keywords: cluster of differentiation 36; kidney metabolism; lipoprotein lipase