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

Puntip Tantiwong, Karthigayan Shanmugasundaram, Adriana Monroy, Sangeeta Ghosh, Mengyao Li, Ralph A. DeFronzo, Eugenio Cersosimo, Apiradee Sriwijitkamol, Sumathy Mohan, Nicolas Musi

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)E794-E801
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume299
Issue number5
DOIs
StatePublished - Nov 2010

Keywords

  • Interleukin-6
  • Monocyte chemotactic protein-1
  • Nuclear factor-κB
  • Skeletal muscle

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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