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Impact of Isoorientin on Metabolic Activity and Lipid Accumulation in Differentiated Adipocytes

Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg 7505, South Africa
Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa 3886, South Africa
Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Tygerberg 7505, South Africa
Department of Life and Environmental Sciences, Polytechnic University of Marche, 60131 Ancona, Italy
Department of Biochemistry, Faculty of Science, University of Johannesburg, Kingsway Campus, Auckland Park 2006, South Africa
Department of Biochemistry, Faculty of Natural and Agricultural Sciences, North West University, Mafikeng Campus, Mmabatho 2735, South Africa
Author to whom correspondence should be addressed.
Molecules 2020, 25(8), 1773;
Received: 1 March 2020 / Revised: 30 March 2020 / Accepted: 1 April 2020 / Published: 13 April 2020
The current study explored the effect of isoorientin on the metabolic activity and lipid accumulation in fully differentiated 3T3-L1 adipocytes. To achieve this, the 3T3-L1 pre-adipocytes were differentiated for eight days and treated with various concentrations of isoorientin (0.1–100 μM) for four hours. Subsequently, the metabolic activity, lipid accumulation, and mitochondrial respiration were assessed. Furthermore, to unravel the molecular mechanisms that might elucidate the bioactivity of isoorientin, protein expression of the genes involved in insulin signaling and energy expenditure, such as AKT and AMPK, were investigated. The results showed that isoorientin, at different doses, could block lipid storage and enhance glycerol release, with a concomitant improvement of the metabolic activity and mitochondrial function. Although the observed beneficial effects of isoorientin on these cultured 3T3-L1 adipocytes were not consistent at all concentrations, it was clear that doses between 1 and 10 μM were most effective compared to the untreated control. Moreover, the activity of isoorientin was comparable to tested positive controls of CL-316,2431, isoproterenol, insulin, and metformin. Mechanistically, protein expression of AKT and AMPK, was enhanced with isoorientin exposure, suggesting their partial role in modulating lipid metabolism and mitochondrial biogenesis. Indeed, our results showed that isoorientin has the ability to enhance mitochondrial respiration, as we observed an increase in the ATP and oxygen consumption rate. Therefore, we concluded that isoorientin has a potential to impact mitochondrial activity, lipid metabolism and energy expenditure using an in vitro experimental model of obesity. View Full-Text
Keywords: isoorientin; obesity; metabolic activity; lipid accumulation; 3T3-L1 adipocytes isoorientin; obesity; metabolic activity; lipid accumulation; 3T3-L1 adipocytes
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Ziqubu, K.; Muller, C.J.F.; Dludla, P.V.; Mthembu, S.X.H.; Obonye, N.; Louw, J.; Kappo, A.P.; Silvestri, S.; Orlando, P.; Tiano, L.; Mazibuko-Mbeje, S.E. Impact of Isoorientin on Metabolic Activity and Lipid Accumulation in Differentiated Adipocytes. Molecules 2020, 25, 1773.

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