Physiological roles of group X-secreted phospholipase A2 in reproduction, gastrointestinal phospholipid digestion, and neuronal function.
Although the secreted phospholipase A(2) (sPLA(2)) family has been generally thought to participate in pathologic events such as inflammation and atherosclerosis, relatively high and constitutive expression of group X sPLA(2) (sPLA(2)-X) in restricted sites such as reproductive organs, the gastrointestinal tract, and peripheral neurons raises a question as to the roles played by this enzyme in the physiology of reproduction, digestion, and the nervous system. Herein we used mice with gene disruption or transgenic overexpression of sPLA(2)-X to clarify the homeostatic functions of this enzyme at these locations. Our results suggest that sPLA(2)-X regulates 1) the fertility of spermatozoa, not oocytes, beyond the step of flagellar motility, 2) gastrointestinal phospholipid digestion, perturbation of which is eventually linked to delayed onset of a lean phenotype with reduced adiposity, decreased plasma leptin, and improved muscle insulin tolerance, and 3) neuritogenesis of dorsal root ganglia and the duration of peripheral pain nociception. Thus, besides its inflammatory action proposed previously, sPLA(2)-X participates in physiologic processes including male fertility, gastrointestinal phospholipid digestion linked to adiposity, and neuronal outgrowth and sensing.
Lipid Metabolism Project, the Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Hiroyasu
H
Sato
Yuki
Y
Isogai
Seiko
S
Masuda
Yoshitaka
Y
Taketomi
Yoshimi
Y
Miki
Daisuke
D
Kamei
Shuntaro
S
Hara
Tetsuyuki
T
Kobayashi
Yukio
Y
Ishikawa
Toshiharu
T
Ishii
Kazutaka
K
Ikeda
Ryo
R
Taguchi
Yoshikazu
Y
Ishimoto
Noriko
N
Suzuki
Yasunori
Y
Yokota
Kohji
K
Hanasaki
Toshiko
T
Suzuki-Yamamoto
Kei
K
Yamamoto
Makoto
M
Murakami
D000818:Animals; D004063:Digestion / Q000502:physiology*; D005260:Female; D041981:Gastrointestinal Tract / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000201:enzymology*; D009928:Organ Specificity; D054497:Phospholipases A2, Secretory / Q000096:biosynthesis* / Q000235:genetics; D010743:Phospholipids / Q000235:genetics / Q000378:metabolism*; D012098:Reproduction / Q000502:physiology*
D010743:Phospholipids; D054497:Phospholipases A2, Secretory
Mech Dev. 1999 Dec;89(1-2):103-14
10559485
Eur J Neurosci. 2006 Feb;23(3):627-36
16487144
Pain. 2001 Sep;93(3):267-277
11514086
Cell. 2008 Sep 19;134(6):914-6
18805083
Exp Neurol. 2008 Aug;212(2):507-14
18565512
Br J Pharmacol. 2001 Jun;133(3):438-44
11375261
J Biol Chem. 2007 Aug 24;282(34):24642-9
17604277
Biochim Biophys Acta. 2006 Jul;1761(7):745-56
16757211
Mol Reprod Dev. 1999 May;53(1):68-76
10230818
Science. 2010 Apr 9;328(5975):228-31
20203013
Diabetes. 2006 Apr;55(4):935-41
16567514
Neuron. 2002 Jan 3;33(1):23-34
11779477
Mol Pharmacol. 2009 Oct;76(4):778-90
19602573
Br J Pharmacol. 1997 Oct;122(4):605-10
9375954
Biochem J. 2005 Apr 1;387(Pt 1):27-38
15509193
J Biol Chem. 2010 Jun 25;285(26):20031-9
20421306
J Immunol. 2007 Oct 1;179(7):4800-7
17878379
Science. 2005 Dec 9;310(5754):1678-80
16339444
J Biol Chem. 2006 Nov 24;281(47):36420-33
17008322
Cell. 1997 Oct 17;91(2):197-208
9346237
Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):726-30
9892701
Biochim Biophys Acta. 2004 Nov 8;1686(1-2):61-76
15522823
J Exp Med. 2007 Apr 16;204(4):865-77
17403936
Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10501-6
10468638
Nat Neurosci. 1999 Dec;2(12):1114-9
10570489
J Biol Chem. 2005 Jun 17;280(24):23203-14
15781456
Biochem J. 2009 Jun 12;421(1):17-27
19371233
J Biol Chem. 2002 Feb 22;277(8):5849-57
11694541
Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6338-43
18430798
Neurosci Res. 2001 Dec;41(4):299-332
11755218
J Biol Chem. 1997 Jun 20;272(25):15745-52
9188469
J Clin Invest. 2001 Feb;107(3):325-31
11160156
Neuroscience. 2008 Jun 26;154(3):1077-87
18511207
Nature. 2000 May 11;405(6783):183-7
10821274
Nature. 2005 May 5;435(7038):104-8
15875025
Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11569-74
11016971
Nature. 1997 Aug 14;388(6643):678-82
9262402
Gastroenterology. 2001 Apr;120(5):1193-202
11266383
Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11563-8
11016970
Biochim Biophys Acta. 2003 Nov 30;1635(1):37-47
14642775
Biochem J. 1999 May 1;339 ( Pt 3):615-20
10215600
Biochim Biophys Acta. 1987 Sep 25;921(2):245-53
3651485
Pain. 2004 Jul;110(1-2):10-21
15275747
Development. 2002 Jun;129(12):2879-89
12050136
Am J Physiol Endocrinol Metab. 2002 Nov;283(5):E994-E1001
12376327
Nature. 2009 Oct 29;461(7268):1282-6
19865172
J Immunol. 2009 Apr 15;182(8):4891-8
19342668
Circulation. 2008 Jun 10;117(23):2977-85
18506007
J Biol Chem. 2008 Nov 28;283(48):33483-97
18801741
J Biol Chem. 2004 Aug 6;279(32):33684-95
15140897
J Neurochem. 2006 Nov;99(3):1000-10
17076662
J Biol Chem. 2006 May 26;281(21):14663-9
16569634
J Clin Invest. 2005 Mar;115(3):673-9
15719070
EMBO Mol Med. 2010 May;2(5):172-87
20432503
Annu Rev Physiol. 1983;45:651-77
6342528
FASEB J. 2010 Jul;24(7):2516-24
20215528
Br J Pharmacol. 2009 Aug;157(7):1263-9
19563529
Prostaglandins Other Lipid Mediat. 2002 Aug;68-69:3-58
12432908
J Biol Chem. 2005 Jul 29;280(30):28044-52
15927955
Neuron. 1997 Mar;18(3):439-51
9115737
FASEB J. 2001 Feb;15(2):312-21
11156947
J Clin Invest. 1996 Jan 1;97(1):250-7
8550843
Annu Rev Biochem. 2008;77:495-520
18405237
J Exp Zool. 1997 Sep 1;279(1):81-8
9285373
Science. 2000 Apr 14;288(5464):306-13
10764638
J Biol Chem. 2002 Aug 9;277(32):29116-24
12021277
Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):12921-6
18728192
Nat Med. 2009 Apr;15(4):442-6
19287392
Nat Med. 2004 Jul;10(7):712-8
15195086
PLoS One. 2007 Feb 14;2(2):e218
17299598
Arterioscler Thromb Vasc Biol. 2007 Mar;27(3):600-6
17204667
J Pharmacol Exp Ther. 2010 May;333(2):540-6
20123931
EMBO J. 2008 Nov 19;27(22):3047-55
18923424
J Clin Invest. 2010 May;120(5):1415-28
20424324
Nat Cell Biol. 2006 Oct;8(10):1143-8
16998478
Neuroscience. 2005;133(2):543-53
15885922
Nature. 2006 Apr 6;440(7085):813-7
16598260
J Biol Chem. 2001 Mar 30;276(13):10083-96
11106649
J Biol Chem. 2004 Apr 16;279(16):16488-94
14761945
FASEB J. 2010 Nov;24(11):4313-24
20585029
J Immunol. 1999 Jun 15;162(12):7402-8
10358193
Endocrinology. 1999 Jan;140(1):310-7
9886840
Arterioscler Thromb Vasc Biol. 1999 May;19(5):1284-90
10323781
Science. 1997 Aug 1;277(5326):681-3
9235889
J Clin Invest. 2010 May;120(5):1400-14
20424323
Atherosclerosis. 2011 Jan;214(1):58-64
20833395