Endocrine Abstracts

Introduction: VEGFA is considered the main angiogenic factor in adipose tissue. It is believed that a low angiogenic capacity may decrease the adipogenic potential and consequently promotes adipocyte hypertrophy, which in turn, is closely related to insulin resistance (IR). Oestradiol (E₂) is a regulator of the VEGFA gene and a protector against obesity. However nothing is known about the E₂ effects on VEGF adipocyte production, and its consequence for cellular sensitivity and much less about the adjacent molecular mechanisms. Thus, the aim of the present work was to investigate the role of E₂ on the VEGFA expression determining the participation of the estrogen receptors ESR1 and ESR2 in this process.

Methods: Differentiated 3T3-L1 adipocytes were treated (24 h) with 10 e 100 nmol/l of 17β-E₂ and/or selective ESR1-agonist PPT, ESR1-antagonist MPP, ESR2-agonist DPN and ESR2-antagonist PHTPP. We analyzed VEGFA mRNA and protein expression by real time PCR and Western blotting, respectively.

Results: E₂ enhanced VEGFA mRNA and protein (20–30%) expression at 10 and 100 nmol/l. Treatment with PPT enhanced VEGFA expression (~30%) in the absence or presence of E₂. However treatment with ESR2 agonist DPN didn’t change VEGFA expression. In addition, the ESR1-antagonist MPP or the ESR2-antagonist PHTPP alone were not able to change the VEGFA expression, but in the presence of E₂ the VEGFA expression was increased (20–30%) in both treatments as compared to control.

Conclusion: The present results reveal that E₂ induced VEGFA production in adipocytes, in part, via activation of ESR1 receptor. However, there is evidence of co-regulation of both receptors, since in the absence of ESR1, high dose of E₂ was able to induce VEGFA expression. Taken together, the increased VEGFA production induced by E₂ in adipocytes can improve the local angiogenesis, protecting the adipose tissue from obesity-induced hypoxia, and consequently, from insulin resistance.

Disclosure: This work was supported by FAPESP #2012/04831-1 #2013/03343-6.