Induction of Sphk1 activity in obese adipose tissue macrophages promotes survival

During obesity, adipose tissue macrophages (ATM) are increased in concert with local inflammation and insulin resistance. Since the levels of sphingolipid (SLs) in adipose tissue (AT) are altered during obesity we investigated the potential impact of SLs on ATMs. For this, we first analyzed expressi...

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Bibliographic Details
Published in:PloS one 2017-07, Vol.12 (7), p.e0182075-e0182075
Main Authors: Gabriel, Tanit L, Mirzaian, Mina, Hooibrink, Berend, Ottenhoff, Roelof, van Roomen, Cindy, Aerts, Johannes M F G, van Eijk, Marco
Format: Article
Language:English
Subjects:
Adipose tissue
Adipose Tissue - cytology
Animals
Biology and Life Sciences
Body fat
CD11b Antigen - metabolism
Cell death
Cell survival
Cell Survival - drug effects
Cell Survival - physiology
Cells, Cultured
Chloroquine
Chloroquine - pharmacology
Cluster Analysis
Diet, High-Fat - adverse effects
Endoplasmic reticulum
Gene expression
Genes
Health aspects
Insulin
Insulin resistance
Kinases
Lipids
Macrophages
Macrophages - drug effects
Macrophages - metabolism
Male
Medicine and Health Sciences
Mice
Mice, Inbred C57BL
Mice, Obese
Obesity
Obesity - metabolism
Palmitic acid
Palmitic Acid - pharmacology
Phosphotransferases (Alcohol Group Acceptor) - genetics
Phosphotransferases (Alcohol Group Acceptor) - metabolism
RAW 264.7 Cells
Research and Analysis Methods
Sphingolipids - metabolism
Sphingosine kinase
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Summary:During obesity, adipose tissue macrophages (ATM) are increased in concert with local inflammation and insulin resistance. Since the levels of sphingolipid (SLs) in adipose tissue (AT) are altered during obesity we investigated the potential impact of SLs on ATMs. For this, we first analyzed expression of SL metabolizing genes in ATMs isolated from obese mice. A marked induction of sphingosine kinase 1 (Sphk1) expression was observed in obese ATM when compared to lean ATM. This induction was observed in both MGL-ve (M1) and MGL1+ve (M2) macrophages from obese WAT. Next, RAW264.7 cells were exposed to excessive palmitate, resulting in a similar induction of Sphk1. This Sphk1 induction was also observed when cells were treated with chloroquine, a lysosomotropic amine impacting lysosome function. Simultaneous incubation of RAW cells with palmitate and the Sphk1 inhibitor SK1-I promoted cell death, suggesting a protective role of Sphk1 during lipotoxic conditions. Interestingly, a reduction of endoplasmic reticulum (ER) stress related genes was detected in obese ATM and was found to be associated with elevated Sphk1 expression. Altogether, our data suggest that lipid overload in ATM induces Sphk1, which promotes cell viability.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0182075