NF-κB activity in muscle from obese and type 2 diabetic subjects under basal and exercise-stimulated conditions.
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.
Tantiwong
Puntip
P
Texas Diabetes Institute, University of Texas Health Science Center at San Antonio, USA.
Shanmugasundaram
Karthigayan
K
Monroy
Adriana
A
Ghosh
Sangeeta
S
Li
Mengyao
M
DeFronzo
Ralph A
RA
Cersosimo
Eugenio
E
Sriwijitkamol
Apiradee
A
Mohan
Sumathy
S
Musi
Nicolas
N
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D053181:Caspase 8 / Q000096:biosynthesis / Q000235:genetics; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D015444:Exercise / Q000502:physiology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D010101:Oxygen Consumption; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D001786:Blood Glucose; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; C505530:CASP8 protein, human; D053181:Caspase 8