Central melanocortin stimulation increases phosphorylated perilipin A and hormone-sensitive lipase in adipose tissues.
Norepinephrine (NE) released from the sympathetic nerves innervating white adipose tissue (WAT) is the principal initiator of lipolysis in mammals. Central WAT sympathetic outflow neurons express melanocortin 4-receptor (MC4-R) mRNA. Single central injection of melanotan II (MTII; MC3/4-R agonist) nonuniformly increases WAT NE turnover (NETO), increases interscapular brown adipose tissue (IBAT) NETO, and increases the circulating lipolytic products glycerol and free fatty acid. The WAT pads that contributed to this lipolysis were inferred from the increases in NETO. Because phosphorylation of perilipin A (p-perilipin A) and hormone-sensitive lipase are necessary for NE-triggered lipolysis, we tested whether MTII would increase these intracellular markers of lipolysis. Male Siberian hamsters received a single 3rd ventricular injection of MTII or saline. Trunk blood was collected at 0.5, 1.0, and 2.0 h postinjection from excised inguinal, retroperitoneal, and epididymal WAT (IWAT, RWAT, and EWAT, respectively) and IBAT pads. MTII increased circulating glycerol concentrations at 0.5 and 1.0 h, whereas free fatty acid concentrations were increased at 1.0 and 2.0 h. Western blot analysis showed that MTII specifically increased p-perilipin A and hormone-sensitive lipase only in fat pads that previously had MTII-induced increases in NETO. Phosphorylation increased in IWAT at all time points and IBAT at 0.5 h, but not RWAT or EWAT at any time point. These results show for the first time in rodents that p-perilipin A can serve as an in vivo, fat pad-specific indictor of lipolysis and extend our previous findings showing that central melanocortin stimulation increases WAT lipolysis.
Shrestha
Y B
YB
Department of Biology, Georgia State University, Atlanta, Georgia 30302-4010, USA.
Vaughan
C H
CH
Smith
B J
BJ
Song
C K
CK
Baro
D J
DJ
Bartness
T J
TJ
D000273:Adipose Tissue / Q000294:innervation / Q000378:metabolism* / Q000502:physiology; D002001:Adipose Tissue, Brown / Q000378:metabolism; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins; D000697:Central Nervous System Stimulants / Q000378:metabolism; D006224:Cricetinae; D004822:Epididymis / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism; D005990:Glycerol / Q000097:blood / Q000378:metabolism; D008066:Lipolysis / Q000502:physiology*; D008297:Male; D053486:Melanocortins / Q000378:metabolism; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism; D010456:Peptides, Cyclic; D000070778:Perilipin-1; D017111:Phodopus; D010750:Phosphoproteins; D010766:Phosphorylation; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics / Q000378:metabolism; D002787:Sterol Esterase / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000502:physiology; D000521:alpha-MSH / Q000031:analogs & derivatives
D002352:Carrier Proteins; D000697:Central Nervous System Stimulants; D005230:Fatty Acids, Nonesterified; D053486:Melanocortins; D010456:Peptides, Cyclic; D000070778:Perilipin-1; D010750:Phosphoproteins; D044105:Receptor, Melanocortin, Type 4; C079282:melanotan-II; D000521:alpha-MSH; D002787:Sterol Esterase; D005990:Glycerol; D009638:Norepinephrine
Am J Physiol. 1999 Jun;276(6):R1569-78
10362733
Best Pract Res Clin Endocrinol Metab. 2005 Dec;19(4):471-82
16311212
J Biol Chem. 1991 Jun 15;266(17):11341-6
2040638
Obes Res. 2005 Apr;13(4):653-61
15897473
J Lipid Res. 2001 Apr;42(4):536-44
11290825
J Clin Invest. 1995 Mar;95(3):1109-16
7883959
Horm Metab Res. 2009 Oct;41(10):736-40
19585405
Peptides. 2006 Feb;27(2):281-90
16434123
Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):12035-9
7505452
Int J Obes Relat Metab Disord. 2000 Nov;24 Suppl 4:S47-52
11126242
Am J Physiol Regul Integr Comp Physiol. 2004 Jan;286(1):R38-45
14500267
Endocrinology. 2007 Nov;148(11):5339-47
17702843
J Biol Chem. 1990 Nov 5;265(31):18769-75
2172232
Endocrinology. 2003 Nov;144(11):4692-7
12960080
Cell Signal. 2006 Apr;18(4):401-8
16182514
Proc Natl Acad Sci U S A. 2001 May 22;98(11):6494-9
11371650
J Biol Chem. 1998 Jan 2;273(1):215-21
9417067
J Biol Chem. 1999 Apr 23;274(17):12017-22
10207024
Pharmacol Res. 2006 Jun;53(6):482-91
16644234
J Lipid Res. 2007 Jun;48(6):1273-9
17401109
Endocrinology. 1996 May;137(5):2043-50
8612546
Am J Physiol. 1995 Mar;268(3 Pt 2):R744-51
7900918
Am J Physiol. 1998 Nov;275(5):R1399-411
9791054
Life Sci. 2000 Jun 16;67(4):437-45
11003053
Am J Physiol Regul Integr Comp Physiol. 2008 Aug;295(2):R417-28
18550869
Nat Genet. 2000 Dec;26(4):474-9
11101849
Diabetes. 2004 May;53(5):1261-70
15111495
J Neuroendocrinol. 2003 Feb;15(2):173-81
12535159
J Biol Chem. 2006 Jun 9;281(23):15837-44
16595669
J Lipid Res. 2007 Dec;48(12):2547-59
17878492
Am J Physiol. 1998 Jul;275(1):R291-9
9688991
J Neurosci. 1997 Sep 1;17(17):6597-610
9254672
J Lipid Res. 1973 Nov;14(6):672-7
4742561
Am J Physiol Endocrinol Metab. 2007 Jun;292(6):E1847-55
17327373
Acta Physiol Scand. 2003 Mar;177(3):351-7
12609006
Ann N Y Acad Sci. 2003 Jun;994:74-83
12851300
J Biol Chem. 2000 Dec 8;275(49):38486-93
10948207
J Physiol. 2009 Jul 1;587(Pt 13):3393-404
19417097
Proc Nutr Soc. 2005 Feb;64(1):53-64
15877923
J Biol Chem. 2006 Apr 28;281(17):11901-9
16488886
J Cell Biol. 2003 Jun 23;161(6):1093-103
12810697
FEBS Lett. 1998 Sep 11;435(1):125-9
9755872
J Mol Endocrinol. 2004 Feb;32(1):145-53
14765998
Am J Physiol Regul Integr Comp Physiol. 2005 Nov;289(5):R1467-76
16221982
Biochem Soc Trans. 2003 Dec;31(Pt 6):1120-4
14641008
Mol Pharmacol. 2008 Jan;73(1):215-23
17911533
J Biol Chem. 2005 Dec 30;280(52):43109-20
16243839
Ann N Y Acad Sci. 1999 Nov 18;892:155-68
10842661
J Biol Chem. 2004 Sep 10;279(37):38236-48
15208325
Obes Res. 1995 Nov;3 Suppl 4:507S-514S
8697051
Diabetes. 2005 Nov;54(11):3190-7
16249444
J Physiol. 1999 Dec 1;521 Pt 2:545-52
10581323
J Biol Chem. 2003 Mar 7;278(10):8401-6
12477720
Am J Physiol Regul Integr Comp Physiol. 2008 May;294(5):R1445-52
18321949
J Lipid Res. 2007 Aug;48(8):1655-72
17460327
J Clin Invest. 2007 Nov;117(11):3475-88
17885689
Peptides. 1986 Nov-Dec;7(6):1079-85
3562318
J Clin Invest. 1978 Mar;61(3):714-21
641150
J Biol Chem. 1998 Sep 18;273(38):24665-9
9733764
Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8537-41
1528859