Exercise reverses high-fat diet-induced impairments on compartmentalization and activation of components of the insulin-signaling cascade in skeletal muscle.
The aims of this investigation were 1) to determine whether endurance exercise training could reverse impairments in insulin-stimulated compartmentalization and/or activation of aPKCzeta/lambda and Akt2 in skeletal muscle from high-fat-fed rodents and 2) to assess whether the PPARgamma agonist rosiglitazone could reverse impairments in skeletal muscle insulin signaling typically observed after high-fat feeding. Sprague-Dawley rats were placed on chow (NORCON, n = 16) or high-fat (n = 64) diets for 4 wk. During a subsequent 4-wk experimental period, high-fat-fed rats were allocated (n = 16/group) to either sedentary control (HFC), exercise training (HFX), rosiglitazone treatment (HFRSG), or a combination of both exercise training and rosiglitazone (HFRX). Following the 4-wk experimental period, animals underwent hindlimb perfusions. Insulin-stimulated plasma membrane-associated aPKCzeta and -lambda protein concentration, aPKCzeta/lambda activity, GLUT4 protein concentration, cytosolic Akt2, and aPKCzeta/lambda activities were reduced (P < 0.05) in HFC compared with NORCON. Cytosolic Akt2, aPKCzeta, and aPKClambda protein concentrations were not affected in HFC compared with NORCON. Exercise training reversed the deleterious effects of the high-fat diet such that insulin-stimulated compartmentalization and activation of components of the insulin-signaling cascade in HFX were normalized to NORCON. High-fat diet-induced impairments to skeletal muscle glucose metabolism were not reversed by rosiglitazone administration, nor did rosiglitazone augment the effect of exercise. Our findings indicate that chronic exercise training, but not rosiglitazone, reverses high-fat diet induced impairments in compartmentalization and activation of components of the insulin-signaling cascade in skeletal muscle.
Yaspelkis
Ben B
BB
Exercise Biochemistry Laboratory, Dept. of Kinesiology, California State University Northridge, 18111 Nordhoff St., Northridge, CA 91330-8287, USA. ben.yaspelkis@csun.edu
Lessard
Sarah J
SJ
Reeder
Donald W
DW
Limon
Jose J
JJ
Saito
Misato
M
Rivas
Donato A
DA
Kvasha
Ilya
I
Hawley
John A
JA
D000273:Adipose Tissue / Q000033:anatomy & histology / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002451:Cell Compartmentation / Q000187:drug effects; D004036:Diet, Atherogenic; D004822:Epididymis / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D045162:Thiazolidinediones / Q000494:pharmacology
D007004:Hypoglycemic Agents; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D010750:Phosphoproteins; D045162:Thiazolidinediones; D000077154:Rosiglitazone; C494923:Akt2 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D011493:Protein Kinase C