ABSTRACT

Dietary Conjugated Linoleic Acid Normalizes Impaired Glucose Tolerance in the Zucker Diabetic Fatty fa/faRat Karen L. Houseknecht, Purdue University; John P. Vanden Heuvel, Pennsylvania State University; Silvia Y. Moya-Camarena, Carla P. Portocarrero, Louise W. Peck, Kwangok P. Nickel, and Martha Belury, Purdue University.

Conjugated linoleic acid (CLA) is a naturally occurring fatty acid found in meat which has anti-carcinogenic and anti-antherogenic properties. CLA activates PPAR-alpha in liver, and shares functional similarities to ligands of PPAR-gamma, the thiazolidinediones, which are potent insulin sensitizers. We provide the first evidence that CLA is able to normalize impaired glucose tolerance and improve hyperinsulinemia in the pre-diabetic ZDF rat. Additionally, dietary CLA increased steady state levels of aP2 mRNA in adipose tissue of fatty ZDF rats compared to controls, consistent with activation of PPAR-gamma. The insulin sensitizing effects of CLA are due, at least in part, to activation of PPAR-gamma since increasing levels of CLA induced a dose-dependent transactivation of PPAR-gamma in CV-1 cells cotransfected with PPAR-gamma and PPRE X 3-luciferase reporter construct. CLA effects on glucose tolerance and glucose homeostasis indicate that dietary CLA may prove to be an important therapy for the prevention and treatment of NIDDM.