Tumor Necrosis Factor α Produces Insulin Resistance in Skeletal Muscle by Activation of Inhibitor κB Kinase in a p38 MAPK-dependent Manner

Álvaro, Cristina de; Teruel, Teresa; Hernández, Rosario; Lorenzo, Margarita

doi:10.1074/jbc.m312021200

Cited by 352 publications

(253 citation statements)

References 50 publications

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“…Akt also inhibits myonuclear apoptosis and muscle protein degradation by inactivating Bad [76] and the FoxO transcription factor [77], respectively. Insulin-stimulated Akt activation is significantly decreased in advanced age in the rat skeletal muscle [78], as a result of TNF-α-induced insulin resistance[79]. …”

Section: The Involvement Of Apoptosis In the Pathogenesis Of Sarcopeniamentioning

confidence: 99%

Multiple Pathways to the Same End: Mechanisms of Myonuclear Apoptosis in Sarcopenia of Aging

Marzetti

Privitera

Simili

et al. 2010

The Scientific World JOURNAL

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Sarcopenia, the age-related decline in muscle mass and function, represents a significant health issue due to the high prevalence of frailty and disability associated with this condition. Nevertheless, the cellular mechanisms responsible for the loss of muscle mass in old age are still largely unknown. An altered regulation of myocyte apoptosis has recently emerged as a possible contributor to the pathogenesis of sarcopenia. Studies in animal models have shown that the severity of skeletal muscle apoptosis increases over the course of aging and correlates with the degree of muscle mass and strength decline. Several apoptotic pathways are operative in aged muscles, with the mitochondria- and TNF-α-mediated pathways likely being the most relevant to sarcopenia. However, despite the growing number of studies on the subject, a definite mechanistic link between myocyte apoptosis and age-related muscle atrophy has not yet been established. Furthermore, the evidence on the role played by apoptosis in human sarcopenia is still sparse. Clearly, further research is required to better define the involvement of myocyte apoptosis in the pathogenesis of muscle loss at advanced age. This knowledge will likely help in the design of more effective therapeutic strategies to preserve muscle mass into old age, thus fostering independence of the elderly population and reducing the socioeconomic burden associated with sarcopenia.

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Section: The Involvement Of Apoptosis In the Pathogenesis Of Sarcopeniamentioning

confidence: 99%

Multiple Pathways to the Same End: Mechanisms of Myonuclear Apoptosis in Sarcopenia of Aging

Marzetti

Privitera

Simili

et al. 2010

The Scientific World JOURNAL

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“…Furthermore, nearly threefold elevated levels of tumor necrosis factor-α (TNF-α) messenger RNA are reported in hemiparetic quadriceps muscle from patients with stroke compared with those from nonparetic legs and nonstroke control subjects [34]. Elevated TNF-α levels in skeletal muscle tissue are strongly linked to muscular wasting and insulin resistance in T2DM and advancing age and may contribute to the structural and metabolic abnormalities in hemiparetic skeletal muscle after stroke [35][36][37][38]. Since exercise training has been shown to reduce skeletal muscle TNF-α expression, which improves muscle strength and metabolic function in selected nonstroke populations [36], modification of inflammatory pathways through exercise therapy warrants consideration in the high CVD risk stroke population.…”

Section: Tissue-level Abnormalities After Strokementioning

confidence: 99%

Task-oriented treadmill exercise training in chronic hemiparetic stroke

Ivey

Hafer‐Macko²,

Macko³

2008

JRRD

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Abstract-Patients with stroke have elevated hemiparetic gait costs secondary to low activity levels and are often severely deconditioned. Decrements in peak aerobic capacity affect functional ability and cardiovascular-metabolic health and may be partially mediated by molecular changes in hemiparetic skeletal muscle. Conventional rehabilitation is time delimited in the subacute stroke phase and does not provide adequate aerobic intensity to reverse the profound detriments to fitness and function that result from stroke. Hence, we have studied progressive full body weight-support treadmill (TM) training as an adjunct therapy in the chronic stroke phase. Task-oriented TM training has produced measurable changes in fitness, function, and indices of cardiovascular-metabolic health after stroke, but the precise mechanisms for these changes remain under investigation. Further, the optimal dose of this therapy has yet to be identified for individuals with stroke and may vary as a function of deficit severity and outcome goals. This article summarizes the functional and metabolic decline caused by inactivity after stroke and provides current evidence that supports the use of TM training during the chronic stroke phase, with protocols and inclusion/exclusion criteria described. Our research findings are discussed in relation to associated research.Key words: aerobic activity, ambulatory function, cardiovascular disease risk, exercise training, hemiplegia, metabolic health, physical deconditioning, rehabilitation, stroke, treadmill. PROBLEM OF POSTSTROKE DECONDITIONINGStroke is a leading cause of disability [1][2][3][4], with residual neurological deficits that persistently impair function and lead to profound physical deconditioning [5][6]. By limiting mobility and increasing fall risk, the hemiparetic gait that accompanies chronic stroke promotes a sedentary lifestyle, which leads to disability through deconditioning and "learned non-use" [7][8]. Peak cardiovascular fitness levels following hemiparetic stroke are roughly half those of age-matched sedentary individuals [5,[9][10]. Further, the energy requirements of hemiparetic gait are elevated by 55 to 100 percent compared with age-matched control subjects [11][12]. This detrimental combination of poor peak exercise capacity and elevated energy demands for hemiparetic gait is termed diminished physiological fitness reserve [13]. The cardiovascular deconditioning coupled with the secondary body composition abnormalities that follow stroke Abbreviations: ACSM = American College of Sports Medicine, ADL = activities of daily living, BMI = body mass index, CVD = cardiovascular disease, ECG = electrocardiogram, HR = heart rate, HRR = HR reserve, IGT = impaired glucose tolerance, MHC = myosin heavy chain, T2DM = type 2 diabetes mellitus, TM = treadmill, TNF-α = tumor necrosis factor-α, WIQ = Walking Impairment Questionnaire, VA = Department of Veterans Affairs, VO 2 = peak oxygen consumption.

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“…[39][40][41] In addition to adiponectin-related mechanisms, a number of proinflammatory cytokines including TNF-α, IL-1 and IL-6 have each been suggested to have a role in insulin resistance via the downregulation of GLUT 4 gene transcription and translocation, as well as the inhibition of insulin receptors by mechanisms related to the upregulation of the suppressors of cytokine signaling proteins. 42,43 Insulin resistance may in turn result in elevated blood glucose concentrations placing excess strain on the kidneys and ultimately resulting in tissue damage and further inflammation. Atherosclerotic plaques associated with cardiovascular disease are also influenced by, and further induce, elevations in proinflammatory mediators.…”

Section: Chronic Inflammation Following Scimentioning

confidence: 99%

Immune dysfunction and chronic inflammation following spinal cord injury

2014

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Study design: Review article. Objectives: The objective of this study is to provide an overview of the many factors that contribute to the chronic inflammatory state typically observed following spinal cord injury (SCI). Methods: Literature review. Results: Not applicable. Conclusion: SCI is typically characterized by a low-grade inflammatory state due to a number of factors. As bidirectional communication exists between the nervous, endocrine and immune systems, damage to the spinal cord may translate into both endocrinal and immune impairment. Damage to the autonomic nervous system may induce immune dysfunction directly, through the loss of neural innervation of lymphoid organs, or indirectly by inducing endocrinal impairment. In addition, damage to the somatic nervous system and the corresponding loss of motor and sensory function increases the likelihood of developing a number of secondary health complications and metabolic disorders associated with a state of inflammation. Lastly, numerous related disorders associated with a state of chronic inflammation have been found to be at a substantially higher prevalence following SCI. Together, such factors help explain the chronic inflammatory state and immune impairment typically observed following SCI. An understanding of the interactions between systems, both in health and disease, and the many causes of chronic inflammation may aid in the effective future treatment of immune dysfunction and related disorders following SCI.

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Tumor Necrosis Factor α Produces Insulin Resistance in Skeletal Muscle by Activation of Inhibitor κB Kinase in a p38 MAPK-dependent Manner

Cited by 352 publications

References 50 publications

Multiple Pathways to the Same End: Mechanisms of Myonuclear Apoptosis in Sarcopenia of Aging

Multiple Pathways to the Same End: Mechanisms of Myonuclear Apoptosis in Sarcopenia of Aging

Task-oriented treadmill exercise training in chronic hemiparetic stroke

Immune dysfunction and chronic inflammation following spinal cord injury

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