Adiponectin and skeletal muscle: pathophysiological implications in metabolic stress.
Upregulation of muscular adiponectin could act as a local protective mechanism to counteract cellular damage in obesity by weakening inflammation, oxidative stress, and apoptosis. To test this hypothesis, adiponectin-knockout (KO) and wild-type (WT) mice were fed a Western diet (WD). WT mice under WD conditions displayed 63% higher adiponectin expression in myocytes than those under standard laboratory diet (SLD) conditions (P = 0.011). WD-fed KO mice exhibited approximately threefold larger myocyte degeneration than WT mice (P = 0.003). Even under SLD conditions, myotubes of KO mice displayed already moderate immunolabeling for markers of oxidative stress (peroxiredoxin-3/5) and for a lipid peroxidation product (hydroxynonenal). Expression of tumor necrosis factor-α (TNF-α) and caspase-6, a marker of apoptosis, was also present. After WD challenge, immunoreactivity for these markers was strong in muscle of KO mice, although it was detected to a lesser extent in WT mice. Activation of NF-κB and caspase-6 doubled in myocytes of WD-fed KO mice when compared to WT mice (P < 0.001). Furthermore, muscle electrotransfer of the adiponectin gene prevented these abnormalities in WD-fed KO mice. Finally, gene abrogation of the adiponectin receptor 1 (AdipoR1) by siRNA recapitulated a pro-inflammatory state in C2C12 myotubes. Thus, upregulation of muscular adiponectin may be triggered by obesity and be crucial locally to counteract oxidative stress, inflammation, and apoptosis. These effects operate in an autocrine/paracrine manner via AdipoR1 and down-regulation of NF-κB signaling.
Endocrinology, Diabetes and Nutrition Unit, Institute of Experimental and Clinical Research, Medical Sector, University of Louvain, Brussels, Belgium.
Julie
J
Jortay
Maximin
M
Senou
Michel
M
Abou-Samra
Laurence
L
Noel
Annie
A
Robert
Marie-Christine
MC
Many
Sonia M
SM
Brichard
D052242:Adiponectin / Q000235:genetics / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001823:Body Composition / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D053178:Caspase 6 / Q000378:metabolism; D004032:Diet; D018014:Gene Transfer Techniques; D051379:Mice; D018345:Mice, Knockout; D032342:Muscle Cells / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology*; D016328:NF-kappa B / Q000502:physiology; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D018384:Oxidative Stress / Q000502:physiology; D013312:Stress, Physiological / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D052242:Adiponectin; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D053178:Caspase 6