Synergistic effects of conjugated linoleic acid and chromium picolinate improve vascular function and renal pathophysiology in the insulin-resistant JCR:LA-cp rat.
OBJECTIVE
Conjugated linoleic acid (CLA) is a natural constituent of dairy products, specific isomers of which have recently been found to have insulin sensitizing and possible antiobesity actions. Chromium is a micronutrient which, as the picolinate (CrP), has been shown to increase insulin sensitivity in animal models, including the JCR:LA-cp rat. We tested the hypothesis that these agents may have beneficial synergistic effects on the micro- and macrovasculopathy associated with hyperinsulinaemia and early type 2 diabetes.


METHODS
Insulin-resistant cp/cp rats of the JCR:LA-cp strain were treated with mixed isomers of CLA (1.5% w/w in the chow) and/or CrP at 80 microg/kg/day (expressed as Cr) from 4 weeks of age to 12 weeks of age. Plasma insulin, lipid and adiponectin levels, aortic vascular function, renal function and glomerular sclerosis were assessed.


RESULTS
CLA administration reduced food intake, body weight and fasting insulin in JCR:LA-cp rats. Plasma adiponectin levels were significantly elevated in rats treated with both CLA and CrP. Aortic hypercontractility was reduced and the relaxant response to the nitric oxide-releasing agent acetylcholine (Ach) was increased in CrP-treated rats. Striking reductions were also observed in the level of urinary albumin and the severity of glomerular sclerosis in rats treated specifically with CLA.


CONCLUSIONS
CLA and CrP have beneficial effects ameliorating several of the pathophysiologic features of an insulin-resistant rat model. These supplements may be useful adjuncts in the management of patients with the metabolic syndrome and warrant further study.
Proctor
S D
SD
Metabolic and Cardiovascular Diseases Laboratory, Alberta Institute for Human Nutrition, 4-10 Agriculture Forestry Centre, University of Alberta, Edmonton, AB, Canada.
Kelly
S E
SE
Stanhope
K L
KL
Havel
P J
PJ
Russell
J C
JC
D052242:Adiponectin / Q000097:blood; D000419:Albuminuria / Q000188:drug therapy; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology; D001835:Body Weight / Q000187:drug effects; D003928:Diabetic Nephropathies / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004435:Eating / Q000187:drug effects; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy / Q000503:physiopathology*; D010848:Picolinic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D046509:Tissue Culture Techniques; D014661:Vasoconstriction / Q000187:drug effects*
D052242:Adiponectin; D007328:Insulin; D044243:Linoleic Acids, Conjugated; D010848:Picolinic Acids; C030614:picolinic acid