Menadione and iron overload trigger neutral lipid remodeling in adipocytes and adipose tissue.

FUNK MELANIA; MANISCALCHI A; BENZI JUNCOS O; ALZA, N; CONDE, MELISA A.; SALVADOR GABRIELA; URANGA, R

Virtual

Congreso; SAIB-SAMIGE 2021,; 2021

SAIB-SAMIGE

99.M.I. Funk, A. Maniscalchi, O.N. Benzi Juncos, N.P. Alza, M.A. Conde, G.A. Salvador, R.M. Uranga. SAIB-SAMIGE Joint meeting 2021, Noviembre de 2021A growing body of evidence indicates that oxidative stress (OS) can cause an increase in the preadipocyte proliferation, and in the adipocyte differentiation. However, the biochemical mechanisms by which OS alters adipocyte neutral lipid metabolism are not completely elucidated. Menadione and iron (Fe) overload are well known OS enhancers through induction of Fenton and Haber Weiss reactions. We have previously demonstrated that menadione exposure (20 and 50 µM) in differentiated 3T3-L1 adipocytes results in increased cell oxidant levels and in the downregulation of adipogenic genes and transcription factors. Our goal in this work was to investigate the effect of menadione and Fe overload in neutral lipid metabolism both in adipocytes cell culture and by using an in vivo model. For this purpose, we worked with differentiated adipocytes challenged with menadione and with C57BL/6 mice exposed to Fe overload. Differentiated 3T3-L1 adipocytes were exposed to menadione for 24 h and then neutral lipid profile was analyzed. For the in vivo OS model, Fe-saccharate (800 or 1332 mg/kg) or vehicle were administrated by intraperitoneal injection (four-dose scheme in 16 days). Plasma, visceral and gonadal adipose tissue obtained from Fe-treated animals and controls were used to determine OS markers and to characterize neutral lipid profile. We found that in adipocytes menadione-induced OS increased triglyceride content and activated lipolysis. In mice, lipid peroxide levels and conjugated dienes derived from fatty acid oxidation were increased in visceral and gonadal adipose tissue after Fe-treatment. No changes were detected in catalase activity. OS markers from plasma were also increased by Fe-overload. Monoacylglycerol and diacylglycerol levels were decreased, and no difference was observed in triacylglycerol levels in Fe-overloaded mice. Fe treatment caused a diminution in the wet weight of both gonadal and visceral adipose tissues when compared to control animals. Consequently, the ratio triacylglycerol/g wet tissue was increased by the effect of OS. Together, our results demonstrate that different OS inducers promote an active remodeling of neutral lipid in adipose tissue.