Dietary Corosolic Acid Ameliorates Obesity and Hepatic Steatosis

Banaba leaves (Lagerstroemia speciosa LINN.) have been used as a traditional medicine in Southeast Asia, and tea made from the leaves is used as a treatment for diabetes. The leaves contain large amounts of corosolic acid (CRA) (Fig. 1), which recently has attracted attention for its biological properties It was shown that Banaba leaf extract (1% CRA) treatment for 2 weeks decreased blood glucose levels in humans. In addition, CRA (10mg) has been shown to reduce post challenge plasma glucose levels at 90min in humans. We previously reported that CRA ameliorates hypertension and abnormal lipid metabolism as well as mitigating oxidative stress and the inflammatory state in SHR/NDmcrcp rats on a high fat diet) that is an animal model of metabolic syndrome.) We also found that the administration of CRA (10mg/kg) in a normal diet for 2 weeks improved hyperglycemia by reducing insulin resistance in a KK-Ay mouse, an obese animal model that spontaneously develops hypertriglyceridemia, hyperglycemia, hyperinsulinemia, and diabetes.) However, the effects of CRA on the adipocytokines and transcription factors that play central roles in the development of obesity are unknown.
Obesity and type 2 diabetes in both humans and animals are associated with insulin resistance.) Adiponectin is an insulin-sensitizing hormone, and plasma levels of adiponectin have been reported to be significantly reduced in obese /diabetic mice and humans.) It also was reported that adiponectin receptors, AdipoR1 and AdipoR2, are downregulated in adipose tissue and skeletal muscle in obese diabetic ob/ob mouse, which is correlated with decreased adiponectin sensitivity.)
Abnormalities of lipid metabolism are frequently observed in obesity and type 2 diabetes. Peroxisome proliferator-activated receptor (PPAR)a is predominantly expressed in liver, and regulates the expression of genes involved in lipid metabolism. Activators of PPARa decrease circulating lipid levels and are commonly used to treat hypertriglyceridemia and other dyslipidemic states. Recent studies suggest that the activation of PPARa prevents high fat diet-induced obesity,) insulin resistance) and hepatic steatosis.) It was also found that activation of PPARa increased AdipoR1 and AdipoR2 expression in adipocytes in vivo.)
Growth and differentiation of adipocytes are regulated by PPARg, which is highly expressed in adipose tissue. Activation of PPARg by agonists such as thiazolidinediones increases the number of small adipocytes, which increases the amount of the insulin-sensitizing hormone adiponectin.PPARg activation also stimulates lipid storage in adipocytes and reduces lipotoxicity in liver and skeletal muscle, thereby improving insulin sensitivity.

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