(P31-016-23) Arsenic Induces Mitochondrial Dysfunction and Reduces Glycolitic Metabolism in Visceral Adipocytes of Obese Mice

Objectives: Arsenic exposure is a health problem in many countries. Previously, we have shown that arsenic increased food efficiency of HFD in mice. Arsenic also decreased the amount of mRNA of fatty oxidative genes (CPT1α and PPARα) in retroperitoneal adipose tissue (rVAT) of lean or obese mice, whereas rVAT fatty acid oxidation activity was reduced only in mice fed high-fat diet (HFD) exposed to arsenic, suggesting a decrease on mitochondrial function. Thus, our objective was to evaluate the in vitro effect of arsenic on mitochondrial function and glycolytic metabolism in adipocytes of lean and obese mice.

Methods: Stromal Vascular Fraction-preadipocytes from visceral rVAT of C57BL/6 lean and obese mice were differentiated into adipocytes and exposed in vitro to 1 μM sodium arsenite for 72 h. Adipocytes viability was monitored by non-polar lipids and DNA staining with BODIPY and Hoechst, respectively. Mitochondrial function and glycolysis were determined through a mitochondrial stress test by measurement of oxygen consumption rate and extracellular acidification rate in a Seahorse XF Analyzer (Agilent). Mitochondria amount was quantified by MitoTracker Red CMXRos probe.

Results: Beside the viability of adipocytes after arsenic exposure was above 90%, arsenic decreased maximal respiration and reserve respiratory capacity in adipocytes from lean mice in a similar magnitude that a HFD did. However, in adipocytes from obese mice arsenic diminished these two parameters even more together with a significant reduction of basal respiration, ATP-production associated respiration, proton leak, and non-mitochondrial respiration. Surprisingly, arsenic did not modify mitochondrial amount. Finally, arsenic exposure also decreased basal glycolysis and glycolytic capacity in adipocytes from obese mice.

Conclusions: Arsenic reduced glycolytic metabolism and mitochondrial function in a non-cytotoxic dose in retroperitoneal adipocytes of obese mice.

Funding Sources: Conacyt and DGAPA (UNAM), México