Effects of peroxisome proliferator-activated receptor delta on placentation, adiposity, and colorectal cancer.

Proc Natl Acad Sci U S A 2002 Jan 26;99(1):303-8. Epub 2001 Dec 26.

Gene Expression Laboratory, Howard Hughes Medical Institute, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.

Targeting of the nuclear prostaglandin receptor peroxisome proliferator-activated receptor delta (PPARdelta) by homologous recombination results in placental defects and frequent (>90%) midgestation lethality. Surviving PPARdelta(-/-) mice exhibit a striking reduction in adiposity relative to wild-type levels. This effect is not reproduced in mice harboring an adipose tissue-specific deletion of PPARdelta, and thus likely reflects peripheral PPARdelta functions in systemic lipid metabolism. Finally, we observe that PPARdelta is dispensable for polyp formation in the intestine and colon of APC(min) mice, inconsistent with its recently proposed role in the establishment of colorectal tumors. Together, these observations reveal specific roles for PPARdelta in embryo development and adipocyte physiology, but not cancer.

Download full-text PDF

Source
http://www.pnas.org/cgi/doi/10.1073/pnas.012610299
Publisher Site
http://dx.doi.org/10.1073/pnas.012610299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC117556PMC
January 2002
3 Reads

Publication Analysis

Top Keywords

proliferator-activated receptor
8
peroxisome proliferator-activated
8
receptor delta
8
ppardelta
5
ppardelta functions
4
peripheral ppardelta
4
reflects peripheral
4
ppardelta reflects
4
functions systemic
4
lipid metabolism
4
finally observe
4
observe ppardelta
4
metabolism finally
4
deletion ppardelta
4
systemic lipid
4
adipose tissue-specific
4
adiposity relative
4
reduction adiposity
4
striking reduction
4
exhibit striking
4

Altmetric Statistics

References

(Supplied by CrossRef)

Mangelsdorf et al.
Cell 1995

Kliewer et al.
PNAS 1994

Kliewer et al.
Recent Progress in Hormone Research 2001

Pineda Torra et al.
Current opinion in lipidology 1999

Tontonoz et al.
Cell 1994

Barak et al.
Molecular cell 1999

Tontonoz et al.
Cell 1998

Chawla et al.
Molecular cell 2001

Lehmann et al.
Journal of Biological Chemistry 1995

Forman et al.
Cell 1995

PNAS 2001

Similar Publications