1521-P: Carnosic Acid Protects against Diet-Induced Insulin Resistance

Background: Obesity and type 2 diabetes (T2D) are associated with elevated plasma free fatty acids (FFA). In vivo exposure to FFAs, such as palmitate, by lipid infusion results in insulin resistance as observed in obesity and T2D. In recent years, compounds found in herbs and plants have attracted attention for prevention and treatment of insulin resistance and T2D. In recent studies by our group, carnosic acid (CA), found in rosemary, increased glucose uptake and attenuated the FFA (palmitate)-induced insulin resistance in muscle cells and adipocytes. In addition, CA caused a robust activation of AMP-activated protein kinase (AMPK). Our present study aimed to examine the effects of CA on mice fed a high-fat high sucrose diet (HFSD), which mimics the Western-style diet.

Material and Methods: C57Bl/6J mice (4 week old) were given control diet (CTD) or HFSD for 8 weeks, which we have seen induces fasting and fed hyperglycemia and insulin resistance during an insulin tolerance test (ITT). CA (70 mg/kg/day) or vehicle were administered orally (incorporated into the diet) for 8 weeks in combination with HFSD. Results: Mice underwent intraperitoneal insulin tolerance test (ipITT) and intraperitoneal glucose tolerance test (ipGTT). Preliminary data from the ipITT revealed that the HFSD+CA group had similar insulin tolerance to that of the CTD group. Indeed, the AUC of the ipITT of the CA HFSD (mean + SEM, 632 + 75) group was significantly lower than that of the HFSD (1000 + 118) group (p<0.05) and similar to CTD (623 + 57) group. In contrast, the ipGTT revealed that the HFSD+CA group had a tendency to better glucose tolerance than the WT HFSD group, but the effect was not significant.

Conclusions: Our data indicate that CA has the potential to counteract diet-induced insulin resistance but is less effective on diet-induced glucose intolerance.