PPARs: Nuclear Receptors Controlled by, and Controlling, Nutrient Handling through Nuclear and Cytosolic Signaling.
Peroxisome proliferator-activated receptors (PPARs), which are known to regulate lipid homeostasis, are tightly controlled by nutrient availability, and they control nutrient handling. In this paper, we focus on how nutrients control the expression and action of PPARs and how cellular signaling events regulate the action of PPARs in metabolically active tissues (e.g., liver, skeletal muscle, heart, and white adipose tissue). We address the structure and function of the PPARs, and their interaction with other nuclear receptors, including PPAR cross-talk. We further discuss the roles played by different kinase pathways, including the extracellular signal-regulated kinases/mitogen-activated protein kinase (ERK MAPK), AMP-activated protein kinase (AMPK), Akt/protein kinase B (Akt/PKB), and the NAD+-regulated protein deacetylase SIRT1, serving to control the activity of the PPARs themselves as well as that of a key nutrient-related PPAR coactivator, PPARgamma coactivator-1alpha (PGC-1alpha). We also highlight how currently applied nutrigenomic strategies will increase our understanding on how nutrients regulate metabolic homeostasis through PPAR signaling.
Moreno
Maria
M
Dipartimento di Scienze Biologiche ed Ambientali, Università degli Studi del Sannio, Via Port'Arsa 11, 82100 Benevento, Italy.
Lombardi
Assunta
A
Silvestri
Elena
E
Senese
Rosalba
R
Cioffi
Federica
F
Goglia
Fernando
F
Lanni
Antonia
A
de Lange
Pieter
P
Mol Endocrinol. 1997 Jun;11(6):779-91
9171241
Diabetologia. 2001 Dec;44(12):2220-6
11793024
Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15712-7
14660788
Mol Endocrinol. 2003 Jul;17(7):1240-54
12730331
Nat Genet. 2002 Oct;32(2):245-53
12219087
EMBO J. 2007 Apr 4;26(7):1913-23
17347648
Cell Metab. 2009 Apr;9(4):327-38
19356714
Am J Physiol Cell Physiol. 2009 Jan;296(1):C116-23
19005163
Int J Mol Med. 2000 Jul;6(1):73-81
10851270
J Biol Chem. 1997 Aug 8;272(32):20108-17
9242684
Diabetes. 2001 Feb;50(2):411-7
11272155
Cell. 1999 Apr 16;97(2):161-3
10219237
Endocrinology. 2001 Oct;142(10):4195-202
11564675
Nature. 2007 Jun 21;447(7147):1012-6
17554339
Reprod Toxicol. 2009 Jun;27(3-4):246-257
18996469
Mol Cell Endocrinol. 2006 Aug 15;256(1-2):23-33
16806672
Nature. 1996 Dec 5;384(6608):458-60
8945471
Mol Endocrinol. 2003 Oct;17(10):1944-58
12843208
J Biol Chem. 2007 Jul 6;282(27):19313-20
17500064
J Biol Chem. 1999 Jun 4;274(23):16147-52
10347167
Life Sci. 2009 Jul 17;85(3-4):161-6
19467247
BMC Genomics. 2009 Dec 11;10:596
20003344
Mol Cell Biol. 1998 Jun;18(6):3483-94
9584188
J Biol Chem. 1999 Mar 19;274(12):7681-8
10075656
Diabetologia. 2002 May;45(5):740-3
12107756
Prog Lipid Res. 2001 Jul;40(4):269-81
11412892
Nature. 1998 Sep 10;395(6698):137-43
9744270
Proc Natl Acad Sci U S A. 2009 Jul 7;106(27):11288-93
19549853
Mol Endocrinol. 2003 Jul;17(7):1255-67
12730332
J Biol Chem. 2009 Jul 24;284(30):19945-52
19491097
Nature. 1992 Aug 27;358(6389):771-4
1324435
Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9793-8
18599449
FEBS Lett. 2008 Jan 9;582(1):46-53
18036349
Curr Opin Biotechnol. 1999 Dec;10(6):564-70
10600688
Mol Cell. 1999 Mar;3(3):397-403
10198642
Diabetes. 1997 Aug;46(8):1319-27
9231657
FASEB J. 2006 Dec;20(14):2579-81
17065218
J Clin Invest. 2006 Jul;116(7):1776-83
16823475
Nature. 2001 Sep 13;413(6852):131-8
11557972
Mol Cell Biol. 2009 Dec;29(23):6257-67
19805517
J Clin Invest. 2005 Apr;115(4):1006-15
15761495
PLoS One. 2008 Feb 27;3(2):e1681
18301758
Cell. 2008 Aug 8;134(3):405-15
18674809
Endocrinology. 1996 Oct;137(10):4499-502
8828512
J Biol Chem. 1997 Jul 25;272(30):18779-89
9228052
Biochem Soc Trans. 2003 Feb;31(Pt 1):224-7
12546690
Diabetes. 2005 Apr;54(4):1157-63
15793256
J Mol Endocrinol. 2010 Mar;44(3):143-54
19741045
Science. 1995 Nov 24;270(5240):1354-7
7481822
Nature. 2003 May 29;423(6939):550-5
12754525
Physiol Genomics. 2010 Mar 3;41(1):42-52
20009009
Nature. 2002 Jan 17;415(6869):268-9
11796987
Mol Cell Biol. 1995 Jan;15(1):351-7
7799943
PLoS Biol. 2005 Apr;3(4):e101
15760270
Annu Rev Med. 2002;53:409-35
11818483
Nature. 1997 May 1;387(6628):43-8
9139820
Biofactors. 2009 Sep-Oct;35(5):417-28
19626697
Nature. 2004 Jun 17;429(6993):771-6
15175761
J Biol Chem. 2008 Dec 12;283(50):34896-906
18930917
Nat Struct Mol Biol. 2008 Sep;15(9):924-31
19172745
PLoS One. 2009 Sep 16;4(9):e7046
19756148
PPAR Res. 2008;2008:172676
18815630
J Endocrinol. 2010 Feb;204(2):93-104
19770177
Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7567-71
8755515
Endocr Rev. 2003 Feb;24(1):78-90
12588810
Am J Physiol Endocrinol Metab. 2006 Oct;291(4):E807-16
16720625
Mol Cell. 1999 Oct;4(4):597-609
10549291
J Mol Endocrinol. 2004 Oct;33(2):533-44
15525607
Nature. 2005 Mar 3;434(7029):113-8
15744310
Mol Cell. 2001 Nov;8(5):971-82
11741533
Biochemistry. 1993 Jun 1;32(21):5598-604
7684926
Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11836-41
12189208
Cell Metab. 2006 Jun;3(6):429-38
16753578
Endocrinology. 2007 Aug;148(8):4064-72
17478558
Cell Metab. 2009 Mar;9(3):252-64
19254570
Cell Metab. 2008 Oct;8(4):333-41
18840364
Am J Physiol Endocrinol Metab. 2004 Nov;287(5):E888-95
15292030
Mol Cell Biol. 2006 Aug;26(15):5698-714
16847324
Mol Cell Biol. 2009 Aug;29(15):4091-102
19451226
EMBO J. 1995 Aug 1;14(15):3741-51
7641693
Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15924-9
14676330
PLoS Biol. 2004 Oct;2(10):e294
15328533
Mol Cell Biol. 2007 Mar;27(6):2359-71
17220280
Genes Dev. 2005 Jun 15;19(12):1466-73
15964996
J Physiol. 2006 Aug 15;575(Pt 1):291-303
16763003
Microbiol Mol Biol Rev. 2004 Jun;68(2):320-44
15187187
Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11593-7
8524810
Cell. 2003 Apr 18;113(2):159-70
12705865
Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2613-8
11867749
J Endocrinol. 2010 Jul;206(1):75-83
20453075