Impact of obesity and leptin on protein expression profiles in mouse colon.
BACKGROUND
Elevated leptin levels in obesity are associated with increased risk of colon pathology, implicating leptin signaling in colon disease. However, leptin-regulated processes in the colon are currently uncharacterized. Previously, we demonstrated that leptin receptors are expressed on colon epithelium and that increased adiposity and elevated plasma leptin in rats are associated with perturbed metabolism in colon tissue. Thus, we hypothesize that obesity disrupts expression of proteins regulated by leptin in the colon.


METHODS
A proteomic analysis was conducted to investigate firstly, differences in the colon of mice lacking leptin and leptin signaling (ob/ob and db/db, respectively) by comparing protein expression profiles with wild-type mice. Secondly, responses to leptin challenge in wild-type mice and ob/ob mice were compared to identify leptin-regulated proteins and associated cellular processes.


RESULTS
Forty proteins were identified with significantly altered expression patterns associated with differences in leptin status in comparisons between all groups of mice. These proteins are associated with calcium binding, cell cycle, cell proliferation, electron transport chain, energy metabolism, protein folding and transport, redox regulation, structural proteins, and proteins involved in transport and regulation of mucus production.


CONCLUSIONS
This study provides evidence that obesity and leptin significantly alter protein profiles of a number of proteins linked to cellular processes in colon tissues that may be linked to the increased risk of colon pathology associated with obesity.
Padidar
Sara
S
Molecular Nutrition Group, Rowett Institute of Nutrition and Health, University of Aberdeen, Greenburn Road, Bucksburn, Aberdeen, AB21 9SB, Scotland, UK.
Farquharson
Andrew J
AJ
Williams
Lynda M
LM
Hoggard
Nigel
N
Reid
Martin D
MD
Duncan
Gary J
GJ
Drew
Janice E
JE
D000818:Animals; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D020869:Gene Expression Profiling; D020738:Leptin / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism*; D040901:Proteomics; D054411:Receptors, Leptin / Q000378:metabolism
D020738:Leptin; D054411:Receptors, Leptin
Cell. 2001 Jan 12;104(1):119-30
11163245
Oncogene. 2006 Jan 12;25(2):260-70
16170352
J Cell Biochem. 2005 Jan 1;94(1):178-93
15526283
Biochem Pharmacol. 2006 Jul 14;72(2):204-16
16730665
Am J Physiol Endocrinol Metab. 2008 Jul;295(1):E17-28
18445751
J Biol Chem. 2003 Aug 29;278(35):33120-6
12805373
Am J Physiol Gastrointest Liver Physiol. 2007 Oct;293(4):G682-91
17656443
Cancer Res. 2001 Feb 15;61(4):1375-81
11245437
Biochim Biophys Acta. 2000 Dec 20;1498(2-3):169-73
11108960
J Biol Chem. 1996 May 10;271(19):11059-62
8626647
Endocrinology. 1999 Mar;140(3):1151-7
10067838
J Immunol. 2008 Oct 1;181(7):5035-44
18802107
Am J Physiol Endocrinol Metab. 2006 Jan;290(1):E1-E8
16339923
J Clin Invest. 1995 Jul;96(1):132-40
7615783
Gastroenterol Jpn. 1993 Oct;28(5):647-56
7693537
Br J Cancer. 2008 Jan 29;98(2):426-33
18071363
Carcinogenesis. 2009 Nov;30(11):1832-40
19520793
Gastroenterology. 2004 Feb;126(2):499-510
14762787
Biochim Biophys Acta. 2006 May-Jun;1761(5-6):599-617
16781888
J Immunol. 2006 Dec 1;177(11):8148-53
17114490
FASEB J. 2004 Apr;18(6):696-8
14977884
Inflamm Bowel Dis. 2004 Sep;10(5):584-92
15472519
Inflamm Bowel Dis. 2006 Feb;12(2):100-5
16432373
J Cell Biochem. 2008 Jan 1;103(1):78-97
17497683
Genes Cells. 2009 Feb;14(2):179-89
19170765
Biochim Biophys Acta. 2008 Sep;1782(9):532-41
18598761
J Biol Chem. 1993 May 15;268(14):10582-7
8486711
Am J Physiol Endocrinol Metab. 2005 May;288(5):E973-9
15613679
Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10695-9
12136128
J Clin Endocrinol Metab. 2004 Feb;89(2):748-55
14764791
Diabetes. 1995 Dec;44(12):1438-46
7589852
J Clin Pathol. 2007 Aug;60(8):902-6
17660334
J Pathol. 2004 Nov;204(4):377-85
15495267