Aspalathin, a natural product with the potential to reverse hepatic insulin resistance by improving energy metabolism and mitochondrial respiration.
Sithandiwe E Mazibuko-MbejePhiwayinkosi Vusi DludlaRabia JohnsonElizabeth JoubertJohan LouwKhanyisani ZiqubuLuca TianoSonia SilvestriPatrick OrlandoAndy R OpokuChristo J F MullerPublished in: PloS one (2019)
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 5'-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.
Keyphrases
- protein kinase
- insulin resistance
- blood glucose
- glycemic control
- type diabetes
- pi k akt
- cell cycle arrest
- oxidative stress
- adipose tissue
- signaling pathway
- high fat diet
- metabolic syndrome
- induced apoptosis
- fatty acid
- polycystic ovary syndrome
- cell proliferation
- risk factors
- liver injury
- blood pressure
- human health
- endoplasmic reticulum stress
- drug induced
- structural basis
- tyrosine kinase
- climate change