Kidney triglyceride accumulation in the fasted mouse is dependent upon serum free fatty acids

Diego Scerbo, Ni Huiping Son, Alaa Sirwi, Lixia Zeng, Kelli M. Sas, Vincenza Gifarelli, Gabriele Schoiswohl, Lesley Ann Huggins, Namrata Gumaste, Yunying Hu, Subramaniam Pennathur, Nada A. Abumrad, Erin E. Kershaw, M. Mahmood Hussain, Katalin Susztak, Ira J. Goldberg

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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 glycosphingo-lipid 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)36 mRNA 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.

Original languageEnglish
Pages (from-to)1132-1142
Number of pages11
JournalJournal of lipid research
Volume58
Issue number6
DOIs
StatePublished - Jun 2017

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