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)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.
Highlights
Lipid accumulation is a pathological feature of every type of kidney injury
To assess which lipid pathways were changed in kidneys from fasted animals, mRNAs of proteins involved in fatty acid oxidation (FAO), de novo lipid synthesis, and lipid transport pathways were analyzed by RNA sequencing of whole kidney from fed and fasted mice. mRNA levels of genes that mediate de novo lipogenesis were decreased, including Fasn, squalene epoxidase (Sqle), acetyl-CoA carboxylase (Acaca), and sterol regulatory element-binding transcription factor 1 (Srebf1) and 2 (Fig. 2A)
Intracellular lipases needed to utilize triglyceride stored in lipid droplets increased; hormone sensitive lipase (Hsl/Lipe) mRNA increased 7-fold and adipose triglyceride lipase (Atgl/Pnpla2) 2-fold
Summary
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. 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.—Scerbo, D., N-H. Neutral lipid accumulation occurs during fasting [9] In many tissues, such as the heart, muscle, and Abbreviations: AAKO, Adipose-Atgl knock out; Acsl, acetyl-CoA synthetase long-chain 1; Angptl, angiopoietin-like 4; ATGL, adipose triglyceride lipase; CD, cluster of differentiation; CKD, chronic kidney disease; Cpt1a, carnitine palmitoyltransferase 1; DEG, differentially expressed gene; FAO, fatty acid oxidation; FATP, fatty acid transport protein; HSL, hormone sensitive lipase; iLpl / , inducible-Lpl / ; L-Mttp / , liverspecific knockdown of microsomal triglyceride transfer protein; Lrp, LDL receptor related protein; MTTP, microsomal triglyceride transfer protein; MTTPi, microsomal triglyceride transfer protein inhibitor; P407, poloxamer 407; Plin, perilipin
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
