Chronic TNF-α Neutralization Does Not Improve Insulin Resistance or Endothelial Function in “Healthy” Men with Metabolic Syndrome

Wascher, Thomas C.; Lindeman, J.; Sourij, Harald; Kooistra, Teake; Pacini, Giovanni; Roden, Michael

doi:10.2119/molmed.2010.00221

Cited by 91 publications

(61 citation statements)

References 31 publications

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“…Of note, in patients with spondyloarthritis, anti-TNFa therapy contributed to an early significant increase in both visceral and subcutaneous abdominal adipose tissue after 1-2 years of treatment [98]. Moreover, in a prospective, randomized, double-blind, placebo-controlled pilot study of insulin-resistant obese men, chronic TNFa neutralization by infliximab did not improve insulin resistance and questioned the suggested causative link between adiposity and insulin resistance, at least in human disease [99].…”

Section: Tnfamentioning

confidence: 99%

Adipokines in health and disease

Faßhauer

Blüher

2015

Trends in Pharmacological Sciences

793

664

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Section: Tnfamentioning

confidence: 99%

Adipokines in health and disease

Faßhauer

Blüher

2015

Trends in Pharmacological Sciences

793

664

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“…In contrast to these reports, treatment with anti-TNFα antibodies such as infliximab or etanercept has not been associated with changes in insulin sensitivity and obesity in humans [55–60]. In a recent study, chronic TNF-α neutralization by infliximab led to improvements in inflammatory status, but did not improve insulin resistance or endothelial function in healthy, but obese, insulin-resistant volunteers [57]. Moreover, these studies question the concept that TNF-α is a causative link between obesity and insulin resistance.…”

Section: Tnfαmentioning

confidence: 99%

Adipokines – removing road blocks to obesity and diabetes therapy

Blüher

2014

Molecular Metabolism

224

177

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Prevention of obesity and therapeutic weight loss interventions have provided only limited long term success. Therefore there is an urgent need to develop novel pharmacological treatment strategies, which target mechanisms underlying positive energy balance, excessive fat accumulation and adverse fat distribution. Adipokines may have potential for future pharmacological treatment strategies of obesity and metabolic diseases, because they are involved in the regulation of appetite and satiety, energy expenditure, endothelial function, blood pressure, insulin sensitivity, adipogenesis, fat distribution and insulin secretion and others. There are important road blocks on the way from an adipokine candidate to the clinical use a therapeutic compound. Such road blocks include an incomplete understanding of the mechanism of action, resistance to a specific adipokine, side effects of the adipokine and others. This review focuses on the potential of selected adipokines as therapeutic tools or targets and discusses important road blocks, which currently prevent their clinical use.

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“…However, these beneficial metabolic effects using anti-TNF treatment could not be proven to be successful in obese Zucker rats [191] or recent clinical studies [192]. On the other hand, there are studies reporting improvements in insulin sensitivity or hyperglycemia in insulin A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 22 resistant individuals during prolonged treatment with TNFα targeting strategies infliximab [91] or etanercept [92].…”

Section: Tnfα and Il-1βmentioning

confidence: 99%