title: Differential effects of safflower oil versus fish oil feeding on insulin-stimulated glycogen synthesis, glycolysis, and pyruvate dehydrogenase flux in skeletal muscle: a 13C nuclear magnetic resonance study.
abstract: To examine the effects of safflower oil versus fish oil feeding on in vivo intramuscular glucose metabolism and relative pyruvate dehydrogenase (PDH) versus tricarboxylic acid (TCA) cycle flux, rats were pair-fed on diets consisting of 1) 59% safflower oil, 2) 59% menhaden fish oil, or 3) 59% carbohydrate (control) in calories. Rates of glycolysis and glycogen synthesis were assessed by monitoring [1-(13)C]glucose label incorporation into [1-(13)C]glycogen, [3-(13)C]lactate, and [3-(13)C]alanine in the hindlimb of awake rats via 13C nuclear magnetic resonance (NMR) spectroscopy during a euglycemic (approximately 6 mmol/l) hyperinsulinemic (approximately 180 microU/ml) clamp. A steady-state isotopic analysis of lactate, alanine, and glutamate was used to determine the relative PDH versus TCA cycle flux present in muscle under these conditions. The safflower oil-fed rats were insulin resistant compared with control and fish oil-fed rats, as reflected by a markedly reduced glucose infusion rate (Ginf) during the clamp (21.4 +/- 2.3 vs. 31.6 +/- 2.8 and 31.7 +/- 1.9 mg x kg(-1) x min(-1) in safflower oil versus control and fish oil groups, respectively, P < 0.006). This decrease in insulin-stimulated glucose disposal in the safflower oil group was associated with a lower rate of glycolysis (21.7 +/- 2.2 nmol x g(-1) x min(-1)) versus control (62.1 +/- 10.3 nmol x g(-1) x min(-1), P < 0.001) and versus fish oil (45.7 +/- 6.7 nmol x g(-1) x min(-1), P < 0.04), as no change in glycogen synthesis (103 +/- 15, 133 +/- 19, and 125 +/- 14 nmol x g(-1) x min(-1) in safflower oil, fish oil, and control, respectively) was detected. The intramuscular triglyceride (TG) content was increased in the safflower oil group (7.3 +/- 0.8 micromol/g) compared with the control group (5.2 +/- 0.8 micromol/g, P < 0.05) and the fish oil group (3.6 +/- 1.1 micromol/g, P < 0.01). Conversely, the percent PDH versus TCA cycle flux was decreased in the safflower oil (43 +/- 8%) versus the control (73 +/- 8%, P < 0.01) and fish oil (64 +/- 6%, P < 0.05) groups. These data suggest that the reduced insulin-stimulated glucose disposal attributed to safflower oil feeding was a consequence of reduced glycolytic flux associated with an increase in relative free fatty acid/ketone oxidation versus TCA cycle flux, whereas fish oil feeding did not alter glucose metabolism and may in part be protective of insulin-stimulated glucose disposal by limiting intramuscular TG deposition.
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8020, USA. jucker@mrcbs.med.yale.edu
authors.forename: B M
authors.initials: BM
authors.lastname: Jucker
authors.forename: G W
authors.initials: GW
authors.lastname: Cline
authors.forename: N
authors.initials: N
authors.lastname: Barucci
authors.forename: G I
authors.initials: GI
authors.lastname: Shulman
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002247:Carbon Isotopes; D005395:Fish Oils / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006003:Glycogen / Q000096:biosynthesis; D006019:Glycolysis / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012450:Safflower Oil / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D002247:Carbon Isotopes; D005395:Fish Oils; D007328:Insulin; D011768:Pyruvate Dehydrogenase Complex; D014280:Triglycerides; D012450:Safflower Oil; D006003:Glycogen; D005947:Glucose