Action of nicotinic acid on the reversion of hypoxic-inflammatory link on 3T3-L1 adipocytes

Author(s)

Nakamichi, Renata ^[1] ; Miranda, Erika Prates ^[1] ; de Vergueiro Lobo, Sylvia Madeira ^[1] ; Tristao, Vivian Regina ^[1] ; Dalboni, Maria Aparecida ^{[2, 1]} ; Redublo Quinto, Beata Marie ^[1] ; Batista, Marcelo Costa ^{[3, 4, 1]}

Affiliation

^[1] Univ Fed Sao Paulo, Dept Med, Div Nephrol, Rua Pedro de Toledo 781, Sao Paulo - Brazil

^[2] Univ Nove Julho, Sao Paulo - Brazil

^[3] Hosp Israelita Albert Einstein, Intens Care Ctr, Dialysis Unit, Sao Paulo - Brazil

^[4] Tufts Univ, Sch Med, Div Nephrol, Boston, MA 02111 - USA

• Document type: Journal article
• Source: LIPIDS IN HEALTH AND DISEASE; v. 15, MAY 10 2016.
• Web of Science Citations: 1

Abstract

Background: Hypoxia resulting from adipocyte expansion is considered the basis of the inflammatory milieu observed in Metabolic Syndrome. Nicotinic acid can act on adipocytes interfering on the inflammatory response. In this study, we investigated the role of HIF-1 alpha (hypoxia-inducible factor -1 alpha) in the inflammatory process induced by hypoxia. The effect of nicotinic acid on the PPARs (peroxisome proliferator-activated receptors) expression during the inflammatory response was assessed over its action under HIF-1 alpha in 3T3-L1 adipocytes submitted to hypoxia. Methods: 3T3-L1 adipocytes were pre-treated with nicotinic acid and incubated under hypoxic conditions. The level of adipokines and HIF-1 alpha were quantified using immunoassays. Adipokine expression was measured using real-time PCR, whereas PPARs and HIF-1 alpha expression were analyzed by western blot. The statistical significance of the differences between variables studied was determined by analysis of variance (ANOVA) complemented by Bonferroni's test. Results: The results demonstrated an increase in leptin and PAI-1 (plasminogen activator inhibitor-1) expression, while adiponectin production decreased under hypoxia. In parallel, induction with hypoxia enhanced HIF-1 alpha expression, despite causing reduced expression of PPAR alpha and PPAR gamma. However, nicotinic acid reversed adipokine modulation under hypoxic conditions, leading to decreased HIF-1 alpha expression and increased PPARs expression. Conclusions: Our findings suggest that nicotinic acid blunt the inflammatory response resulting from hypoxia by the reduction of HIF-1 alpha expression and concomitant increase of PPARs a and gamma expression in 3T3-L1 adipocytes. (AU)

• FAPESP's process: 11/07248-2 - Action of nicotinic acid in adiponectin, leptin and PAI-1 production and in PPAR gamma and PPAR alpha expression in 3T3-L1 adipocytes under oxigen deprivation
• Grantee: Renata Nakamichi
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)