Dietary Corosolic Acid Ameliorates Obesity and Hepatic Steatosis in KK-Ay Mice

Abstract

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. [1][2][3][4][5][6][7] It was shown that Banaba leaf extract (1% CRA) treatment for 2 weeks decreased blood glucose levels in humans. 8) In addition, CRA (10 mg) has been shown to reduce post challenge plasma glucose levels at 90 min in humans. 7) 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, 9) that is an animal model of metabolic syndrome.10) We also found that the administration of CRA (10 mg/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. 11,12) 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.13) Adiponectin is an insulin-sensitizing hormone, and plasma levels of adiponectin have been reported to be significantly reduced in obese /diabetic mice and humans.14-16) 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. 17)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, 18) insulin resistance, 18,19) and hepatic steatosis. 20) It was also found that activation of PPARa increased AdipoR1 and AdipoR2 expression in adipocytes in vivo. 21)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. 15,22) PPARg activation also stimulates lipid storage in adipocytes and reduces lipotoxicity in liver and skeletal muscle, thereby improving insulin sensitivity. 23)In the present study, we examined the inhibitory effects of CRA on the development of obesity and hepatic steatosis in Corosolic acid (CRA), a constituent of Banaba leaves, has been reported to exert anti-hypertension, anti-hyperinsulinemia, anti-hyperglycemi...

Increased Plasma Dipeptidyl Peptidase IV (DPP IV) Activity and Decreased DPP IV Activity of Visceral But Not Subcutaneous Adipose Tissue in Impaired Glucose Tolerance Rats Induced by High-Fat or High-Sucrose Diet

“…6,12,13) Several studies in small rodents have reported that DPP IV inhibitors improved oral glucose tolerance in high-fat diet-fed animals. 6,11) Moreover, it has been confirmed that high-fat dietinduced insulin resistance and glucose intolerance were less prevalent in DPP IV-deficient rats than wild-type rats.…”

Effect of corosolic acid on dietary hypercholesterolemia and hepatic steatosis in KK-Ay diabetic mice

“…Two kinds of specific diet were prepared for this study. One was a high cholesterol diet made of CE-2 (Clea, Japan), 1% cholesterol and 0.5% cholic acid, while the other was the same high cholesterol diet containing 0.023% CA, a dosage similar to that used in previous studies (22,30).…”

“…The hypoglycemic effect of CA has been noted in various experiments (7,14,22,25,29). In addition to the hypoglycemic effect, Yamaguchi et al reported its lowering effect on serum fatty acids in SHR/NDmcr-cp rats (31), while Yamada et al observed that CA reduced fasting plasma and liver triglyceride contents in KK-Ay mice (30). The occurrence of hyperlipidemia is prevalent in more than 30% of all diabetics, two to three times more frequent than in nondiabetic patients (1).…”

Bioactivities of Eriobotrya japonica (Thunb.) Lindl. Leaf and Its Triterpenes

“…Since GOAT recognizes fatty acyl-coenzyme (Co)A molecules, such as octanoyl-, hexanoyl-, and decanoyl-CoA [43], we speculated that the carboxyl group in a molecule is an important functional group for this inhibitory effect. Triterpenes, such as asiatic acid, betulinic acid, corosolic acid, glycyrrhetinic acid, oleanolic acid, and ursolic acid have shown antiobesity effects in mice fed a high-fat diet [44][45][46][47][48][49]. Like fatty acids, these triterpenes also have a carboxyl group in their structure, suggesting that they could also suppress octanoylated ghrelin production.…”