Aspalathin, a natural product with the potential to reverse hepatic insulin resistance by improving energy metabolism and mitochondrial respiration.

Sithandiwe E Mazibuko-Mbeje,Andy R Opoku,Khanyisani Ziqubu,Sonia Silvestri,Rabia Johnson,Patrick Orlando,Elizabeth Joubert,Luca Tiano,Christo J F Muller,Johan Louw,Phiwayinkosi V Dludla,Michael Bader

doi:10.1371/journal.pone.0216172

Abstract

Aspalathin is a rooibos flavonoid with established blood glucose lowering properties, however, its efficacy to moderate complications associated with hepatic insulin resistance is unknown. To study such effects, C3A liver cells exposed to palmitate were used as a model of hepatic insulin resistance. These hepatocytes displayed impaired substrate metabolism, including reduced glucose transport and free fatty acid uptake. These defects included impaired insulin signaling, evident through reduced phosphatidylinositol-4,5-bisphosphate 3-kinase/ protein kinase B (PI3K/AKT) protein expression, and mitochondrial dysfunction, depicted by a lower mitochondrial respiration rate. Aspalathin was able to ameliorate these defects by correcting altered substrate metabolism, improving insulin signaling and mitochondrial bioenergetics. Activation of 5ʹ-adenosine monophosphate-activated protein kinase (AMPK) may be a plausible mechanism by which aspalathin increases hepatic energy expenditure. Overall, these results encourage further studies assessing the potential use of aspalathin as a nutraceutical to improve hepatocellular energy expenditure, and reverse metabolic disease-associated complications.

Highlights

Obesity and dysglycemia, the major characteristic features of the metabolic syndrome, have become prevalent in the general population and are associated with a rapid rise in morbidity and mortality [1, 2]
This study showed that aspalathin can target the liver cells to regulate hepatic cellular metabolism and increase energy expenditure likely by modulating PI3K/protein kinase B (AKT) and 5 ́adenosine monophosphate-activated protein kinase (AMPK) signaling pathways
Before proposals presented in this study are accepted, several issues need to be resolved first. This includes confirming these results in an established in vivo model of insulin resistance. Such information would improve our current understanding on the mechanisms involved in metabolic disease associated liver dysfunction, but would highlight the potential use of aspalathin as a nutraceutical to protect against metabolic diseaserelated complications

Summary

Introduction

The major characteristic features of the metabolic syndrome, have become prevalent in the general population and are associated with a rapid rise in morbidity and mortality [1, 2]. Mostly driven by an imbalance between intake and utilization of metabolic substrates such as carbohydrates and lipids remains a prominent. Aspalathin reverses palmitate induced hepatic insulin resistance. The grant holders acknowledge that opinions, findings and conclusions or recommendations expressed in any publication generated by the NRF and SAMRC supported research are those of the authors, and that the NRF and SAMRC accepts no liability whatsoever in this regard. The funding bodies had no involvement in the following aspects: study design; collection, analysis and interpretation of data; writing of the manuscript; decision to publish the work

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