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.

RESEARCH METHODS AND PROCEDURES

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.

DISCUSSION

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.