title: Metabolic implications of dietary trans-fatty acids.
abstract: Dietary trans-fatty acids are associated with increased risk of cardiovascular disease and have been implicated in the incidence of obesity and type 2 diabetes mellitus (T2DM). It is established that high-fat saturated diets, relative to low-fat diets, induce adiposity and whole-body insulin resistance. Here, we test the hypothesis that markers of an obese, prediabetic state (fatty liver, visceral fat accumulation, insulin resistance) are also worsened with provision of a low-fat diet containing elaidic acid (18:1t), the predominant trans-fatty acid isomer found in the human food supply. Male 8-week-old Sprague-Dawley rats were fed a 10% trans-fatty acid enriched (LF-trans) diet for 8 weeks. At baseline, 3 and 6 weeks, in vivo magnetic resonance spectroscopy (1H-MR) assessed intramyocellular lipid (IMCL) and intrahepatic lipid (IHL) content. Euglycemic-hyperinsulinemic clamps (week 8) determined whole-body and tissue-specific insulin sensitivity followed by high-resolution ex vivo 1H-NMR to assess tissue biochemistry. Rats fed the LF-trans diet were in positive energy balance, largely explained by increased energy intake, and showed significantly increased visceral fat and liver lipid accumulation relative to the low-fat control diet. Net glycogen synthesis was also increased in the LF-trans group. A reduction in glucose disposal, independent of IMCL accumulation was observed in rats fed the LF-trans diet, whereas in rats fed a 45% saturated fat (HF-sat) diet, impaired glucose disposal corresponded to increased IMCLTA. Neither diet induced an increase in IMCLsoleus. These findings imply that trans-fatty acids may alter nutrient handling in liver, adipose tissue, and skeletal muscle and that the mechanism by which trans-fatty acids induce insulin resistance differs from diets enriched with saturated fats.
authors: Cardiovascular and Metabolism Disease Area, Novartis Institutes for Biomedical Research, Inc., Cambridge, Massachusetts, USA.
authors: Suzanne E
authors: SE
authors: Dorfman
authors: Didier
authors: D
authors: Laurent
authors: John S
authors: JS
authors: Gounarides
authors: Xue
authors: X
authors: Li
authors: Tara L
authors: TL
authors: Mullarkey
authors: Erik C
authors: EC
authors: Rocheford
authors: Farid
authors: F
authors: Sari-Sarraf
authors: Erica A
authors: EA
authors: Hirsch
authors: Thomas E
authors: TE
authors: Hughes
authors: S Renee
authors: SR
authors: Commerford
mesh_terms: D050154:Adiposity; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D018752:Diet, Fat-Restricted; D002149:Energy Intake; D004734:Energy Metabolism; D015309:Glucose Clamp Technique; D006003:Glycogen / Q000378:metabolism; D006963:Hyperphagia / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D024821:Metabolic Syndrome / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D019301:Oleic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism*; D009829:Oleic Acids; D011236:Prediabetic State / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D044242:Trans Fatty Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D009829:Oleic Acids; D044242:Trans Fatty Acids; D019301:Oleic Acid; C011459:elaidic acid; D006003:Glycogen