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

Khanyisani Ziqubu,Christo J F Muller,Sithandiwe E Mazibuko-Mbeje,Patrick Orlando,Nnini Obonye,Phiwayinkosi V Dludla,Sinenhlanhla X H Mthembu,Luca Tiano,Johan Louw,Abidemi P Kappo,Sonia Silvestri

doi:10.3390/molecules25081773

Abstract

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.

Highlights

Natural products are considered a safe approach in treating metabolic syndrome [1], and their therapeutic potential against obesity has been extensively reviewed [2,3,4]
All tested concentrations of isoorientin significantly increased glucose uptake when compared to the control (Figure 1b)
AMPK is implicated in insulin-independent glucose uptake, and this process is revised in detail by Hayley et al [34], which looks at various experimental models of insulin resistance

Summary

Introduction

Natural products are considered a safe approach in treating metabolic syndrome [1], and their therapeutic potential against obesity has been extensively reviewed [2,3,4]. A C-glycosyl flavonoid, which is found in rooibos, among other plants, and which displays strong ameliorative effects on obesity-linked complications [5,6]. Of general interest, is evidence showing that plant extracts rich in this glucosyl flavone display enhanced anti-obesity properties, including amelioration of various metabolic complications [9,10,11]. Our previous study [13] showed that an extract of fermented rooibos could block adipogenesis and affect adipocyte metabolism in cultured 3T3-L1 adipocytes. This is especially important, since the Food and Drug Administration (FDA)

Methods

Results

Discussion

Conclusion