Obesity has become a major public health problem of global significance. Today,
aspirin remains the most commonly used medication for the treatment of
pyrexia,
pain,
inflammation and antiplatelet. The present study aims at evaluating the possible existence of a putative p53-dependent pathway underlying the
aspirin-induced inhibition of adipogenesis. Cell migration assay was identified by the ability to migrate through Transwell insert.
Oil Red O staining was employed to quantify adipose accumulation. The concentration of
glucose and
triglyceride were measured by using assay kits. The expression levels of several master regulatory molecules controlling various signal pathways were monitored using the immunoblotting techniques.
Aspirin significantly inhibited preadipocyte migration and adipose accumulation. The p53-p21 signaling and the expression of
differentiation marker glycerol-3-phosphate dehydrogenase were increased in a dose-dependent manner. It indicated that
aspirin induced adipocyte differentiation through p53-p21 pathway. The oncogenic ERK 1/2 MAPK signaling was induced, whereas, the expression of adipogenic markers
peroxisome proliferator-activated receptor γ (PPARγ), adipocyte
fatty acid-binding protein (A-FABP) and inflammatory factors
cyclooxygenase-2 (Cox-2),
tumor necrosis factor α (TNFα) and
inducible nitric oxide synthase (iNOS) were inhibited.
Aspirin negatively regulated the pentose phosphate pathway (PPP) by inhibiting the expression of rate-limiting
enzyme glucose-6-phosphate dehydrogenase. Knockdown the expression of oncogenic ERK 1/2 MAPK by using 10 μM
PD98059 significantly increased
triglyceride synthesis, adipose accumulation and activated PPP, however, decreased
glucose uptake. Diverted the
glucose flux to PPP, rather than increased
glucose uptake, was associated with adipogenesis. Down-regulated the expression of
tumor suppressor p53 by 10 μM
pifithrin-α (PFTα) alone had no effect on adipose accumulation. However, administration of
aspirin accompanied with PFTα abolished
aspirin-induced inhibition of adipogenesis. We demonstrated that
aspirin-induced inhibition of adipogenesis was p53-dependent and associated with inactivation of PPP. Blockade PPP may be a novel strategy for
obesity prevention and
therapy. Moreover, when use
aspirin in therapeutic strategy, the p53 status should be considered.