El?bieta Supruniuk

Poland, Medical University of Bialystok, Poland
Title : Effects of branched chain ?-keto acid dehydrogenase (Bckdh) activation on fatty acid transport and oxidation – a study on the adipocytes differentiated from visceral adipose-derived mesenchymal stem cells (AdMSCs) obtained from lean as well as morbidly obese men with or without metabolic syndrome

Abstract

In past few decades, a strong association of obesity and insulin resistance was demonstrated with increased circulating levels of branched chain amino acids. The study aimed to assess the effect of BCAA catabolism activation on the processes of fatty acid transport and oxidation in adipose-derived mesenchymal stem cells (AdMSC) isolated from visceral adipose tissue. Visceral adipose tissue was obtained from four lean males, three morbidly obese males without the metabolic syndrome and three obese men with metabolic syndrome. Immunophenotypic characterization of AdMSC was performed using flow cytometry. In order to induce BCAA catabolism, differentiated AdMSC were incubated for 72 hours with 40 ?M and 160 ?M of BT2, i.e., the selective inhibitor of Bckdh kinase. The impact of BT2 on fatty acid uptake was examined based on the expression level of transporting proteins (i.e., CD36/SR-B2 and FATP4) and by means of liquid scintillation. The degree of fatty acid oxidation was determined based on the release of CO2 and acid soluble metabolites content in cells incubated with 14C-palmitate for 16 h. Additionally, the level of PGC-1? and ?-HAD were evaluated using real-time PCR and Western Blot techniques. We showed that cells retrieved from obese men had lower total expression of fatty acid transporting proteins, although these differences were less profound when considering only plasmalemmal content of transporters. BT2 reduced the CD36 transcript content in visceral adipocytes. Moreover, the release of acid soluble metabolites was enhanced in adipocytes from morbidly obese patients. ASM content substantially increased in cells treated with 160 ?M of BT2 derived from morbidly obese men. In conclusion, BCAA metabolism activation coincides with reduced import of fatty acids to adipocytes and, in cells obtained from obese individuals, with enhanced level of noncomplete fatty acid oxidation. This work was supported by the National Science Center (Poland) under grant 2020/04/X/NZ3/00406.

Biography

Elzbieta Supruniuk is a research and teaching assistant in the Department of Physiology at Medical University of Bialystok in Poland. She received her PhD degree with a dissertation entitled ‘Effects of the pharmacological stimulation of PGC-1? co-activator on lipid metabolism in skeletal muscle cells’. Her scientific interests concern the relationship between the most important energy substrates (i.e., glucose, fatty acids and amino acids) and their contribution to metabolic disorders. Main techniques applied in the realization of her scientific research involve gas liquid chromatography, high-performance liquid chromatography, liquid scintillation, flow cytometry, immunofluorescence, real-time PCR and Western Blot. Currently, she is the co-author of several original and review articles with a total Impact Factor of 41.106.