Diet-induced obesity alters signalling pathways and induces atrophy and apoptosis in skeletal muscle in a prediabetic rat model.
Pro-inflammatory and stress-activated signalling pathways are important role players in the pathogenesis of obesity and insulin resistance. Obesity and type II diabetes are associated with chronic, low-grade inflammation and elevated tumour necrosis factor-α (TNF-α) levels. There is increasing evidence that TNF-α may play a critical role in skeletal muscle atrophy. However, the effects of obesity-induced insulin resistance on these signalling pathways are poorly understood in skeletal muscle. Therefore, the present study addressed the effects of obesity-induced insulin resistance on the activity of the ubiquitin ligases, nuclear factor-B, p38 MAPK and phosphoinositide 3-kinase signalling pathways in the gastrocnemius muscle and compared these with muscle of standard chow-fed control rats. Male Wistar rats were randomly allocated to a control diet group (standard commercial chow; 60% carbohydrates, 30% protein and 10% fat) or a cafeteria diet group (65% carbohydrates, 19% protein and 16% fat) for 16 weeks. Blood analysis was conducted to determine the impact of the model of obesity on circulating insulin, glucose, free fatty acids, TNF-α and angiotensin II concentrations. The experimental animals were 18% heavier and had 68% greater visceral fat mass than their control counterparts and were dyslipidaemic. Significant increases in the ubiquitin ligase and MuRF-1, as well as in caspase-3 and poly-ADP-ribose polymerase cleavage were observed in the muscle of obese animals compared with the control rats. We propose that dyslipidaemia may be a mechanism for the activation of inflammatory/stress-activated signalling pathways in obesity and type II diabetes, which will lead to apoptosis and atrophy in skeletal muscle.
Department of Physiological Sciences, Matieland, Stellenbosch 7600, South Africa.
Balindiwe
B
Sishi
Benjamin
B
Loos
Beverly
B
Ellis
Wayne
W
Smith
Eugene F
EF
du Toit
Anna-Mart
AM
Engelbrecht
D000222:Adaptation, Physiological; D000818:Animals; D001284:Atrophy; D004041:Dietary Fats / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000473:pathology* / Q000503:physiopathology*; D009765:Obesity / Q000150:complications / Q000503:physiopathology*; D011236:Prediabetic State / Q000150:complications / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
D004041:Dietary Fats; D009124:Muscle Proteins