Isomer-specific Antidiabetic Properties of Conjugated Linoleic Acid. Improved Glucose Tolerance, Skeletal Muscle Insulin Action, and UCP-2 Gene Expression

Diabetes. 2001 May;50(5):1149-57. doi: 10.2337/diabetes.50.5.1149.


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)-gamma 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-gamma 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Animals
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism*
  • Body Weight / drug effects
  • Dietary Supplements
  • Energy Intake / drug effects
  • Fatty Acids, Nonesterified / blood
  • Feeding Behavior / drug effects
  • Gene Expression Regulation / drug effects*
  • Glucose Tolerance Test
  • Insulin / blood
  • Insulin / physiology*
  • Ion Channels
  • Isomerism
  • Leptin / blood
  • Linoleic Acids / administration & dosage
  • Linoleic Acids / pharmacology*
  • Male
  • Membrane Transport Proteins*
  • Mitochondrial Proteins*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / physiology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein-Serine-Threonine Kinases*
  • Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • RNA, Messenger / genetics
  • Rats
  • Rats, Zucker
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Transcription Factors / genetics
  • Transcription, Genetic / drug effects
  • Triglycerides / blood
  • Uncoupling Agents / metabolism
  • Uncoupling Protein 2


  • Blood Glucose
  • Fatty Acids, Nonesterified
  • Insulin
  • Ion Channels
  • Leptin
  • Linoleic Acids
  • Membrane Transport Proteins
  • Mitochondrial Proteins
  • Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • Triglycerides
  • Ucp2 protein, rat
  • Uncoupling Agents
  • Uncoupling Protein 2
  • Phosphatidylinositol 3-Kinases
  • Akt1 protein, rat
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt