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Insulin resistance is a metabolic disorder associated with a wide array of cardiovascular complications. This study aimed to investigate the effect of oleic acid on a dietary model of insulin resistance in mice using high fructose high fat diet (HFrHFD) focusing on the role of β-arrestin signaling in the adipose tissue. Insulin resistance was induced by feeding mice high fructose high fat diet (HFrHFD) for 16 weeks. Oleic acid (40 mg/kg/day) was orally administered for 4 weeks starting at week 13. At the end of experiment, survival curve, body weights (BW), fasting blood glucose, serum insulin and insulin resistance (IR) were measured. Furthermore, adipose tissue levels of β-arrestin2, phosphatidyl inositol 4,5 bisphosphate (PIP2), diacyl glycerol (DAG) and phospho serine 473 of protein kinase B (pS473 Akt) were measured. Results showed that, oleic acid significantly increased survival percentage, BW and fasting blood glucose level compared to HFrHFD fed mice. On the other hand, oleic acid significantly reduced serum insulin level while slightly reduced IR compared to HFrHFD fed mice. In addition, oleic acid significantly increased β-arrestin2, PIP2 and pS473 Akt levels while significantly decreased DAG level in the adipose tissue. In conclusion, although oleic acid significantly improved survival curve and β-arrestin signaling in the adipose tissue, it worsened fasting blood glucose level in HFrHFD fed mice. An effect that may be attributed to reduced insulin secretion without comparable improvement in insulin resistance

Oleic acid antagonizes the action of high fructose high fat diet on insulin secretion and adipose tissue β-arrestin signaling