Down-regulation of microsomal prostaglandin E2 synthase-1 in adipose tissue by high-fat feeding.
OBJECTIVE
Prostaglandin (PG)E2 is a lipid mediator implicated in inflammatory diseases and in the regulation of lipolysis and adipocyte differentiation. This work was, thus, undertaken to study the regulation of the various PGE2 synthases (PGESs) in obesity.


METHODS
C57Bl/6 mice were subjected to a high-fat or regular diet for 12 weeks. The levels of PGE2 in white adipose tissue (WAT) of lean and obese mice were quantified by liquid chromatography-mass spectrometry, and the change in expression of the three major PGES caused by diet-induced obesity was characterized by Western blotting. Human preadipocytes and 3T3-L1 cells were used to assess the expression of microsomal prostaglandin E2 synthase-1 (mPGES-1) during adipogenesis.


RESULTS
mPGES-1, mPGES-2, and cytosolic PGES proteins were all detected in WAT of lean animals. mPGES-1 was expressed at higher levels in WAT than in any other tissues examined and was more abundant (3- to 4-fold) in epididymal (visceral) compared with inguinal (subcutaneous) WAT. Expression of mPGES-1 was also detected in undifferentiated and differentiated 3T3-L1 cells and in human primary subcutaneous preadipocytes at all stages of adipogenesis. The mPGES-1 protein was substantially down-regulated in epididymal and inguinal WAT of obese mice, whereas mPGES-2 and cytosolic PGES remained relatively stable. Concordantly, the PGE2 levels in obese inguinal WAT were significantly lower than those of lean animals.


CONCLUSIONS
These data suggest that mPGES-1 is the major form of PGESs contributing to the synthesis of PGE2 in WAT and that its down-regulation might be involved in the alterations of lipolysis and adipogenesis associated with obesity.
Hétu
Pierre-Olivier
PO
Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research, 16711 Trans-Canada Hwy, Kirkland, Quebec, Canada H9H 3L1.
Riendeau
Denis
D
D041721:3T3-L1 Cells; D050156:Adipogenesis / Q000502:physiology*; D000273:Adipose Tissue / Q000201:enzymology* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D015536:Down-Regulation; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008861:Microsomes / Q000201:enzymology / Q000378:metabolism; D000071876:Prostaglandin-E Synthases; D011897:Random Allocation
D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; C000605863:PTGES2 protein, human; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse; C000605866:Ptges2 protein, mouse