Isomer-Specific Antidiabetic Properties of Conjugated Linoleic Acid
Improved Glucose Tolerance, Skeletal Muscle Insulin Action, and UCP-2 Gene Expression
Improved Glucose Tolerance, Skeletal Muscle Insulin Action, and UCP-2 Gene Expression
Abstract
Conjugated linoleic acid (CLA) isomers have a number of beneficial health effects, as shown in biomedical studies with animal models. Previously, we reported that a mixture of CLA isomers improved glucose tolerance in ZDF rats and activated peroxisome proliferator–activated receptor (PPAR)-γ response elements in vitro. Here, our aim was to elucidate the effect(s) of specific CLA isomers on whole-body glucose tolerance, insulin action in skeletal muscle, and expression of genes important in glucose and lipid metabolism. ZDF rats were fed either a control diet (CON), one of two CLA supplemented diets (1.5% CLA) containing differing isoforms of CLA (47% c9,t11; 47.9% c10,t12, 50:50; or 91% c9,t11, c9,t11 isomers), or were pair-fed CON diet to match the intake of 50:50. The 50:50 diet reduced adiposity and improved glucose tolerance compared with all other ZDF treatments. Insulin-stimulated glucose transport and glycogen synthase activity in skeletal muscle were improved with 50:50 compared with all other treatments. Neither phosphatidlyinositol 3-kinase activity nor Akt activity in muscle was affected by treatment. Uncoupling protein 2 in muscle and adipose tissue was upregulated by c9,t11 and 50:50 compared with ZDF controls. PPAR-γ mRNA was downregulated in liver of c9,t11 and pair-fed ZDF rats. Thus, the improved glucose tolerance in 50:50 rats is attributable to, at least in part, improved insulin action in muscle, and CLA effects cannot be explained simply by reduced food intake.
Footnotes
Address correspondence and reprint requests to Karen L. Houseknecht, Discovery Pharmaceuticals, Pfizer Global Research and Development-Groton Laboratories, MS 8220-2239, Eastern Point Rd., Groton, CT 06340-8002. E-mail: karen_l_houseknecht{at}groton.pfizer.com.
Received for publication 27 September 2000 and accepted in revised form 9 February 2001.
J.W.R. and C.P.P contributed equally to this work.
K.L.H. is employed by Pfizer Inc. (Groton, CT), which manufactures and markets pharmaceuticals related to the treatment of diabetes and its complications.
BAT, brown adipose tissue; CLA, conjugated linoleic acid; CON, control diet; ECL, enhanced chemiluminescence; EDL, extensor digitorum longus; G-6-P, glucose-6-phosphate; KHB, Krebs-Henseleit buffer; NEFA, nonesterified fatty acid; PI, phosphatidylinositol; PPAR, peroxisome proliferator–activated receptor; RT-PCR, reverse transcriptase–polymerase chain reaction; SSC, sodium chloride–sodium citrate; TBST, Tris-buffered saline plus Tween; TG, triglyceride; TZD, thiazolidinedione; UCP, uncoupling protein.
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