Journey from cachexia to obesity by TNF

Argilés, Josep Μ.; López‐Soriano, Joaquín; Busquets, Sílvia; López‐Soriano, Francisco J.

doi:10.1096/fasebj.11.10.9271359

Cited by 127 publications

(94 citation statements)

References 83 publications

(2 reference statements)

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“…The results of our current study, together with previous reports, 2,5,6 show that TNF-a reduces adipose tissue mass through multiple mechanisms including inhibition of lipogenesis, facilitation of lipolysis, suppression of adipogenesis and selective induction of adipocyte apoptosis.…”

Section: Selective Loss Of Adipocytes By Tnf-a M Tamai Et Alsupporting

confidence: 84%

“…Indeed, previous reports showed that TNF-a has the potential to modulate lipogenesis and lipolysis in adipocytes. 2 It is also known that TNF-a inhibits adipogenesis at picomolar concentrations. 5,6 Previous studies showed induction of apoptosis by TNF-a in human and rat adipocytes in primary cultures.…”

Section: Resultsmentioning

confidence: 99%

“…1 The pathogenesis of cachexia is mutlifactorial, but previous reports suggested that inflammatory cytokines, especially tumor necrosis factor-a (TNF-a), have a key role. 2 In cachexia, elevation in plasma levels of TNF-a is often observed. It is believed that the circulating TNF-a causes lipolysis and inhibits lipogenesis, leading to reduction in adipose tissue mass.…”

mentioning

confidence: 99%

“…It is believed that the circulating TNF-a causes lipolysis and inhibits lipogenesis, leading to reduction in adipose tissue mass. 2 However, it is well known that TNF-a has the potential to induce apoptosis in various cell types. 3 TNF-a also affects differentiation of several cells including adipocytes.…”

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confidence: 99%

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Selective deletion of adipocytes, but not preadipocytes, by TNF-α through C/EBP- and PPARγ-mediated suppression of NF-κB

Tamai

Shimada

Hiramatsu

et al. 2010

Laboratory Investigation

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Tumor necrosis factor-a (TNF-a) is a key regulator of adipose tissue mass, but mechanisms underlying this effect have not been fully elucidated. We found that exposure to TNF-a caused a significant decrease in the number of adipocytes, but not preadipocytes. Subsequent experiments revealed that TNF-a selectively deleted adipocytes through induction of apoptosis. Following exposure to TNF-a, rapid activation of nuclear factor-kB (NF-kB) was observed only in preadipocytes, but not in adipocytes. Inhibition of NF-kB rendered preadipocytes susceptible to TNF-a-induced apoptosis, suggesting that different activity of NF-kB is the determinant for the distinct apoptotic responses. During adipocyte differentiation, expression and activity of peroxisome proliferator-activated receptor-g (PPARg) were upregulated. Treatment of preadipocytes with a PPARg agonist attenuated NF-kB activation and rendered the cells vulnerable to TNF-a-induced apoptosis. Conversely, treatment of adipocytes with a PPARg antagonist enhanced NF-kB activation and conferred resistance to TNF-a-induced apoptosis, suggesting involvement of PPARg in the suppression of NF-kB in adipocytes. We also found that, following differentiation, expression and activity of CCAAT/ enhancer binding protein (C/EBP), especially C/EBPa and C/EBPb, were upregulated in adipocytes. Overexpression of individual C/EBPs significantly inhibited activation of NF-kB in preadipocytes. Furthermore, transfection with siRNA for C/EBPa or C/EBPb enhanced activity of NF-kB in adipocytes, suggesting that C/EBP is also involved in the repression of NF-kB in adipocytes. These results suggested novel mechanisms by which TNF-a selectively deletes adipocytes in the adipose tissue. The C/EBP-and PPARg-mediated suppression of NF-kB may contribute to TNF-a-related loss of adipose tissue mass under certain pathological situations, such as cachexia.

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Section: Selective Loss Of Adipocytes By Tnf-a M Tamai Et Alsupporting

confidence: 84%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Selective deletion of adipocytes, but not preadipocytes, by TNF-α through C/EBP- and PPARγ-mediated suppression of NF-κB

Tamai

Shimada

Hiramatsu

et al. 2010

Laboratory Investigation

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“…21 In addition, it is also possible that insulin resistance per se might involve the development of obesity. 22,23 Aberrant production of TNF-a in adipose tissue may inhibit insulin from promoting adipocyte triglyceride stores or adipocyte differentiation. Indeed, gene polymorphisms of TNF have been associated with obesity by many investigators.…”

Section: Discussionmentioning

confidence: 99%

Promoter polymorphism in the macrophage migration inhibitory factor gene is associated with obesity

et al. 2005

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Objective: To explore the association of promoter polymorphisms of macrophage migration inhibitory factor (MIF) gene with obesity. Subjects: In total, 213 nondiabetic Japanese subjects. They were divided into three groups according to World Health Organization definitions: lean (body mass index (BMI) o25 kg/m 2 ), overweight (25pBMIo30 kg/m 2 ) and obese (BMIX30 kg/m 2 ). Methods: We examined two polymorphic loci in the MIF gene in the subjects: a single-nucleotide polymorphism at position À173 (G/C) and a CATT-tetranucleotide repeat polymorphism at position À794, which both can affect promoter activity in different cells. Results: We detected four alleles: 5-, 6-, 7-and 8-CATT at position À794. Genotypes without the 5-CATT allele (X/X, X refers to 6-, 7-or 8-CATT alleles) were more common in obese subjects than in lean or overweight groups (P ¼ 0.013). The X-CATT allele was more frequent in obese subjects than in lean or overweight subjects (P ¼ 0.030). In contrast, À173G/C was not associated with obesity. Among the haplotypes of the two promoter polymorphisms, G/5-CATT ((À173G/C)/(À794[CATT] 5-8 )) was associated with a decreased risk of obesity (P ¼ 0.025) and G/6-CATT with an increased risk of overweight (P ¼ 0.028). Conclusion: Promoter polymorphism in the MIF gene is linked with obesity.

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Cancer cachexia: A therapeutic approach

et al. 2000

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Cancer cachexia is a complex syndrome which occurs in more than two‐thirds of patients who die with advanced cancer. The main components of this pathological state are anorexia and metabolic abnormalities such as glucose intolerance, fat depletion, and muscle protein catabolism among others. The aim of the present study is to review the different therapeutic approaches that have been designed to fight and counteract cancer cachexia. © 2000 John Wiley & Sons, Inc. Med Res Rev, 21, No. 1, 83–101, 2001

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Journey from cachexia to obesity by TNF

Cited by 127 publications

References 83 publications

Selective deletion of adipocytes, but not preadipocytes, by TNF-α through C/EBP- and PPARγ-mediated suppression of NF-κB

Selective deletion of adipocytes, but not preadipocytes, by TNF-α through C/EBP- and PPARγ-mediated suppression of NF-κB

Promoter polymorphism in the macrophage migration inhibitory factor gene is associated with obesity

Cancer cachexia: A therapeutic approach

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