Effects of an enriched orange peel extract (OPE) against type 2 diabetes (T2D) were analyzed in ZDF

rats which were hyperglycemic, dyslipidemic and express pro-inflammatory markers. Glucose related

parameters were lowered in the lean control and metformin group as compared to ZDF vehicle controls.

OPE was well tolerated and induced a decline in fasted blood glucose and increase levels of fed glucose

although to a lesser degree as compared to metformin. However, OPE did not improve glucose tolerance

but showed significantly elevated glucose levels. Furthermore, OPE treatment caused an increase of free

fatty acids in a dose-responsive manner as well as elevated levels of cholesterol and LDL. The analysis of

inflammatory mediators revealed a significant down-regulation of COX-2, ICAM-1, and TNF-˛ in epididymal

adipose tissue in response to OPE to a higher degree as compared to ibuprofen. In whole blood, IL-4

was upregulated in a dose-responsive manner as measured by ELISA. In summary, lipophilic OPE showed

strong anti-inflammatory effects in adipose tissue, ambivalent effects against hyperglycemia, whereas

hyperlipidemia was increased. Our study emphasize the complexity of anti-diabetic regimen suggesting

a treatment with OPE to reduce inflammation in adipose tissue in combination with antidiabetic

therapeutics as promising strategy against T2D.