Cafeteria diet-induced insulin resistance is not associated with decreased insulin signaling or AMPK activity and is alleviated by physical training in rats

TY - JOUR

T1 - Cafeteria diet-induced insulin resistance is not associated with decreased insulin signaling or AMPK activity and is alleviated by physical training in rats

AU - Brandt, Nina

AU - De Bock, Katrien

AU - Richter, Erik

AU - Hespel, Peter

N1 - Keywords: 1-Phosphatidylinositol 3-Kinase; Animals; Biological Transport, Active; Cyclic AMP-Dependent Protein Kinases; Diet; Energy Intake; Glucose; Glucose Tolerance Test; Glucose Transport Proteins, Facilitative; Glycogen; Hindlimb; Immunoblotting; Insulin; Insulin Receptor Substrate Proteins; Insulin Resistance; Male; Muscle, Skeletal; Oncogene Protein v-akt; Physical Conditioning, Animal; Rats; Rats, Wistar; Regional Blood Flow; Signal Transduction

PY - 2010/8

Y1 - 2010/8

N2 - 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 (CAFTR). 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 ∼20% reduction in both basal and insulin-stimulated Akt Ser473 phosphorylation (P = 0.051) in the CAF group, there were no differences in insulin signaling (IR Tyr1150/1151, PI 3-kinase activity, Akt Thr308, TBC1D4 Thr642, GSK3-α/β Ser 21/9) or changes in AMPKα1 or -α2, GLUT4, Munc18c, or syntaxin 4 protein expression or in phosphorylation of AMPK Thr172 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.

AB - 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 (CAFTR). 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 ∼20% reduction in both basal and insulin-stimulated Akt Ser473 phosphorylation (P = 0.051) in the CAF group, there were no differences in insulin signaling (IR Tyr1150/1151, PI 3-kinase activity, Akt Thr308, TBC1D4 Thr642, GSK3-α/β Ser 21/9) or changes in AMPKα1 or -α2, GLUT4, Munc18c, or syntaxin 4 protein expression or in phosphorylation of AMPK Thr172 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.

U2 - 10.1152/ajpendo.00098.2010

DO - 10.1152/ajpendo.00098.2010

M3 - Journal article

C2 - 20484011

SN - 0193-1849

VL - 299

SP - E215-E224

JO - American Journal of Physiology - Endocrinology and Metabolism

JF - American Journal of Physiology - Endocrinology and Metabolism

IS - 2

ER -