title: Cafeteria diet-induced insulin resistance is not associated with decreased insulin signaling or AMPK activity and is alleviated by physical training in rats.
abstract: Excess energy intake via a palatable low-fat diet (cafeteria diet) is known to induce obesity and glucose intolerance in rats. However, the molecular mechanisms behind this adaptation are not known, and it is also not known whether exercise training can reverse it. Male Wistar rats were assigned to 12-wk intervention groups: chow-fed controls (CON), cafeteria diet (CAF), and cafeteria diet plus swimming exercise during the last 4 wk (CAF(TR)). CAF feeding led to increased body weight (16%, P < 0.01) and increased plasma glucose (P < 0.05) and insulin levels (P < 0.01) during an IVGTT, which was counteracted by training. In the perfused hindlimb, insulin-stimulated glucose transport in red gastrocnemius muscle was completely abolished in CAF and rescued by exercise training. Apart from a tendency toward an approximately 20% reduction in both basal and insulin-stimulated Akt Ser(473) phosphorylation (P = 0.051) in the CAF group, there were no differences in insulin signaling (IR Tyr(1150/1151), PI 3-kinase activity, Akt Thr(308), TBC1D4 Thr(642), GSK3-alpha/beta Ser(21/9)) or changes in AMPKalpha1 or -alpha2, GLUT4, Munc18c, or syntaxin 4 protein expression or in phosphorylation of AMPK Thr(172) among the groups. In conclusion, surplus energy intake of a palatable but low-fat cafeteria diet resulted in obesity and insulin resistance that was rescued by exercise training. Interestingly, insulin resistance was not accompanied by major defects in the insulin-signaling cascade or in altered AMPK expression or phosphorylation. Thus, compared with previous studies of high-fat feeding, where insulin signaling is significantly impaired, the mechanism by which CAF diet induces insulin resistance seems different.
authors.affiliation: Molecular Physiology Group, Department of Exercise and Sport Sciences, Copenhagen Muscle Research Centre, University of Copenhagen, 13 Universitetsparken, Copenhagen, Denmark.
authors.forename: Nina
authors.initials: N
authors.lastname: Brandt
authors.forename: Katrien
authors.initials: K
authors.lastname: De Bock
authors.forename: Erik A
authors.initials: EA
authors.lastname: Richter
authors.forename: Peter
authors.initials: P
authors.lastname: Hespel
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004032:Diet; D002149:Energy Intake; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006614:Hindlimb / Q000098:blood supply; D015151:Immunoblotting; D007328:Insulin / Q000502:physiology*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000096:biosynthesis / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D006003:Glycogen; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; D017868:Cyclic AMP-Dependent Protein Kinases; D005947:Glucose