Isomer-specific antidiabetic properties of conjugated linoleic acid. Improved glucose tolerance, skeletal muscle insulin action, and UCP-2 gene expression.
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.
Ryder
J W
JW
Department of Clinical Physiology, Karolinska Institute, Stockholm, Sweden.
Portocarrero
C P
CP
Song
X M
XM
Cui
L
L
Yu
M
M
Combatsiaris
T
T
Galuska
D
D
Bauman
D E
DE
Barbano
D M
DM
Charron
M J
MJ
Zierath
J R
JR
Houseknecht
K L
KL
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D019587:Dietary Supplements; D002149:Energy Intake / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005247:Feeding Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood / Q000502:physiology*; D007473:Ion Channels; D007536:Isomerism; D020738:Leptin / Q000097:blood; D008041:Linoleic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011924:Rats, Zucker; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D014280:Triglycerides / Q000097:blood; D014475:Uncoupling Agents / Q000378:metabolism; D000071246:Uncoupling Protein 2
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007473:Ion Channels; D020738:Leptin; D008041:Linoleic Acids; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014280:Triglycerides; D014475:Uncoupling Agents; D000071246:Uncoupling Protein 2; C000604391:Ucp2 protein, rat; C494920:Akt1 protein, rat