Group X secretory phospholipase A2 negatively regulates adipogenesis in murine models.
Studies in vitro indicate that group X secretory phospholipase A(2) (GX sPLA(2)) potently releases arachidonic acid (AA) and lysophosphatidylcholine from mammalian cell membranes. To define the function of GX sPLA(2) in vivo, our laboratory recently generated C57BL/6 mice with targeted deletion of GX sPLA(2) (GX(-/-) mice). When fed a normal rodent diet, GX(-/-) mice gained significantly more weight and had increased adiposity compared to GX(+/+) mice, which was not attributable to alterations in food consumption or energy expenditure. When treated with adipogenic stimuli ex vivo, stromal vascular cells isolated from adipose tissue of GX(-/-) mice accumulated significantly more (20%) triglyceride compared to cells from GX(+/+) mice. Conversely, overexpression of GX sPLA(2), but not catalytically inactive GX sPLA(2), resulted in a significant 50% reduction in triglyceride accumulation in OP9 adipocytes. The induction of genes encoding adipogenic proteins (PPARγ, SREBP-1c, SCD1, and FAS) was also significantly blunted by 50-80% in OP9 cells overexpressing GX sPLA(2). Activation of the liver X receptor (LXR), a nuclear receptor known to up-regulate adipogenic gene expression, was suppressed in 3T3-L1 and OP9 cells when GX sPLA(2) was overexpressed. Thus, hydrolytic products generated by GX sPLA(2) negatively regulate adipogenesis, possibly by suppressing LXR activation.
Li
Xia
X
Graduate Center for Nutritional Sciences, University of Kentucky Medical Center, Lexington, KY 40536-0200, USA.
Shridas
Preetha
P
Forrest
Kathy
K
Bailey
William
W
Webb
Nancy R
NR
D050156:Adipogenesis / Q000502:physiology*; D050154:Adiposity / Q000235:genetics; D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D015536:Down-Regulation; D005786:Gene Expression Regulation; D054509:Group X Phospholipases A2 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000071518:Liver X Receptors; D008156:Luciferases / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D014280:Triglycerides; D008156:Luciferases; D054509:Group X Phospholipases A2