Isoorientin ameliorates lipid accumulation by regulating fat browning in palmitate-exposed 3T3-L1 adipocytes.

Stimulation of fat browning using natural bioactive products is regarded as one of the promising approaches to treat obesity and insulin resistance. Here, we investigated the physiological effects of isoorientin on glucose uptake and lipid accumulation in insulin resistant 3T3-L1 adipocytes. To achieve this, 3T3-L1 adipocytes were exposed to 0.75 mM palmitate for 24 h, to induce insulin resistance, before treatment with 10 µM isoorientin or the comparative controls such as CL-316,243 (10 µM), pioglitazone (10 µM) and compound C (1 µM) for 4 h. Relevant bioassays and Western blot analysis were conducted on these insulin resistant cells. Our results showed that palmitate exposure could induce insulin resistance and mitochondrial dysfunction as measured by reduction in glucose uptake and impaired mitochondrial bioenergetics parameters. However, treatment with isoorientin reversed these effects by improving glucose uptake, blocking lipid accumulation, and modulating the process of mitochondrial respiration. Mechanistically, isoorientin could mediate lipid metabolism by activating 5' AMP-activated protein kinase (AMPK), while also effectively modulating the expression of genes involved in fat browning such as peroxisome proliferator-activated receptor gamma (PPAR)γ/α and uncoupling protein 1 (UCP1). In conclusion, isoorientin impacts insulin resistance in vitro by improving glucose uptake and mitochondrial function, consistent to modulating the expression of genes involved in energy metabolism and fat browning.