NF-κB activity in muscle from obese and type 2 diabetic subjects under basal and exercise-stimulated conditions

• Published in: American journal of physiology: endocrinology and metabolism Vol. 299; no. 5; pp. E794 - E801
• Main Authors: Tantiwong, Puntip, Shanmugasundaram, Karthigayan, Monroy, Adriana, Ghosh, Sangeeta, Li, Mengyao, DeFronzo, Ralph A., Cersosimo, Eugenio, Sriwijitkamol, Apiradee, Mohan, Sumathy, Musi, Nicolas
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.11.2010
• Subjects: Adult; Blood Glucose - metabolism; Blotting, Western; Caspase 8 - biosynthesis; Caspase 8 - genetics; Chemokine CCL2 - biosynthesis; Chemokine CCL2 - genetics; Diabetes Mellitus, Type 2 - metabolism; Exercise - physiology; Fatty Acids, Nonesterified - blood; Female; Humans; Insulin - blood; Interleukin-6 - biosynthesis; Interleukin-6 - genetics; Male; Middle Aged; Muscle, Skeletal - metabolism; NF-kappa B - metabolism; Obesity - metabolism; Oxygen Consumption; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - chemistry; RNA, Messenger - genetics; Signal Transduction
• DOI: 10.1152/ajpendo.00776.2009
• ISSN: 0193-1849; 1522-1555

NF-κB is a transcription factor that controls the gene expression of several proinflammatory proteins. Cell culture and animal studies have implicated increased NF-κB activity in the pathogenesis of insulin resistance and muscle atrophy. However, it is unclear whether insulin-resistant human subjects have abnormal NF-κB activity in muscle. The effect that exercise has on NF-κB activity/signaling also is not clear. We measured NF-κB DNA-binding activity and the mRNA level of putative NF-κB-regulated myokines interleukin (IL)-6 and monocyte chemotactic protein-1 (MCP-1) in muscle samples from T2DM, obese, and lean subjects immediately before, during (40 min), and after (210 min) a bout of moderate-intensity cycle exercise. At baseline, NF-κB activity was elevated 2.1- and 2.7-fold in obese nondiabetic and T2DM subjects, respectively. NF-κB activity was increased significantly at 210 min following exercise in lean (1.9-fold) and obese (2.6-fold) subjects, but NF-κB activity did not change in T2DM. Exercise increased MCP-1 mRNA levels significantly in the three groups, whereas IL-6 gene expression increased significantly only in lean and obese subjects. MCP-1 and IL-6 gene expression peaked at the 40-min exercise time point. We conclude that insulin-resistant subjects have increased basal NF-κB activity in muscle. Acute exercise stimulates NF-κB in muscle from nondiabetic subjects. In T2DM subjects, exercise had no effect on NF-κB activity, which could be explained by the already elevated NF-κB activity at baseline. Exercise-induced MCP-1 and IL-6 gene expression precedes increases in NF-κB activity, suggesting that other factors promote gene expression of these cytokines during exercise.