Elsevier

Human Immunology

Volume 77, Issue 1, January 2016, Pages 47-53
Human Immunology

Review
The relationship between body weight and inflammation: Lesson from anti-TNF-α antibody therapy

https://doi.org/10.1016/j.humimm.2015.10.008Get rights and content

Abstract

Obesity is associated with many pathological conditions. Tumor Necrosis Factor-α (TNF-α) is one of the key mediators of inflammation involved in the obesity-related insulin resistance development. We aim to review the human evidence useful to clarify the relationship between inflammation and body weight, with particular reference to TNF-α. Genetic polymorphisms and epigenetic factors, such as diet, could affect TNF-α activity. TNF-α is associated with obesity, but also with anorexia and cachexia. Despite the role of TNF-α in obesity-related diseases, anti-TNF-α antibody therapy is associated with an increase in adiposity. In conclusion the reviewed results suggest that inflammation is more likely a consequence rather than a cause of obesity.

Introduction

Obesity is associated with many pathological conditions, such as cancer, metabolic syndrome, cardiovascular and autoimmune diseases [1], [2], [3], [4], [5], [6]. Abdominal obesity and adipose tissue macrophages are involved in the generation of low grade chronic inflammation and insulin resistance [6], [7], [8]. Tumor Necrosis Factor-α (TNF-α) is one of the key mediators of this phenomenon. However, TNF-α is related not only with obesity, but also with both anorexia and cachexia [9], [10], [11], [12]. Genetic polymorphisms and epigenetic factors, such as diet, could affect TNF-α activity [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29]. We aim to review the human evidence useful to clarify the relationship between body weight, inflammation and risk of disease, with particular reference to the effect of anti-TNF-α antibody therapy on body weight.

Section snippets

Body weight and risk of diseases

Relative to normal weight, grades 2 and 3 obesity, but not grade 1 obesity, are associated with significantly higher “all-cause” mortality, whereas overweight is associated with significantly lower mortality [30]. Furthermore, despite obesity is a common comorbidity in critically ill patients, septic shock obese subjects have the lowest mortality followed by overweight patients, while patients with a body mass index (BMI) <25 kg/m2 have the highest mortality [31]. Therefore, BMI alone is not

The relationship between adipose tissue and immune cells

Several chronic inflammatory conditions, including rheumatoid arthritis and Crohn’s disease, are characterized by a selective hypertrophy of the adipose deposits in the proximity of the inflammatory lesions [12]. These deposits could be a source of energy-rich fuels for the cells of the immune system, considering that the activation of the immune system is energetically expensive (about 25% of the basal metabolism) [10]. In fact, the release of lipids from the perinodal fat stores is increased

TNF-α as inflammatory mediator in obesity and cachexia

Despite cachexia and obesity represent divergent states of nutritional imbalance, there is an overlap in the inflammatory mediators and in the insulin resistance, although with opposite connections with the fat mass [51]. TNF-α interferes with the signals of the activated insulin receptor, inducing insulin resistance [7]. Despite it has been suggested that obesity may contribute to the increase of serum TNF-α levels in systemic lupus erythematosus [2], HOMA is higher and positively correlated

The effect of anti-TNF-α antibody treatment on body weight

Anti-TNF-α antibody treatment is used in the management of chronic inflammatory diseases and has been tested also in cancer and metabolic syndrome [25], [26], [42], [61], [62], [63], [64], [65], [66], [67], [68], [69], [70], [71], [72], [73], [74], [75], [76], [77], [78], [79], [80], [81], [82], [83], [84], [85], [86], [87], [88], [89], [90], [91], [92]. The results of the studies on the effect of anti-TNF-α treatment on body weight, with at least 2 weeks of follow up in adults, are described in

Conclusion

In cancer, obesity and chronic diseases such as rheumatoid arthritis, the same mediators of inflammation are continuously activated. However, the tissue source of inflammatory cytokines is different, as well as the energy intake and the physical activity. These differences are responsible for the different body weight. TNF-α is one of the key mediators of the previously suggested maladaptive response to overfeeding, which involves insulin resistance and M1 macrophages [6]. Despite the role of

Acknowledgment

We thank Claudio Andrew Gobbi for English review of the manuscript.

References (100)

  • S. Danilla et al.

    Suction-assisted lipectomy fails to improve cardiovascular metabolic markers of disease: a meta-analysis

    J. Plast. Reconstr. Aesthetic Surg.

    (2013)
  • K.G. Kahl et al.

    Cytokine mRNA expression patterns in the disease course of female adolescents with anorexia nervosa

    Psychoneuroendocrinology

    (2004)
  • L. Rodríguez-Rodríguez et al.

    TNFA -308 (rs1800629) polymorphism is associated with a higher risk of cardiovascular disease in patients with rheumatoid arthritis

    Atherosclerosis

    (2011)
  • R. Saraceno et al.

    Effect of anti-tumor necrosis factor-alpha therapies on body mass index in patients with psoriasis

    Pharmacol. Res.

    (2008)
  • A.W. Armstrong et al.

    The association between psoriasis and obesity: a systematic review and meta-analysis of observational studies

    Nutr. Diabetes

    (2012)
  • N.A. Sinicato et al.

    Obesity and cytokines in childhood-onset systemic lupus erythematosus

    J. Immunol. Res.

    (2014)
  • R.K. Joshi et al.

    Obesity related adipokines and colorectal cancer: a review and meta-analysis

    Asian Pacific J. Cancer Prev.

    (2014)
  • L.F. Van Gaal et al.

    Mechanisms linking obesity with cardiovascular disease

    Nature

    (2006)
  • O. Osborn et al.

    The cellular and signaling networks linking the immune system and metabolism in disease

    Nat. Med.

    (2012)
  • J.I. Odegaard et al.

    Pleiotropic actions of insulin resistance and inflammation in metabolic homeostasis

    Science

    (2013)
  • N. Ouchi et al.

    Adipokines in inflammation and metabolic disease

    Nat. Rev. Immunol.

    (2011)
  • J.P. Després et al.

    Abdominal obesity and metabolic syndrome

    Nature

    (2006)
  • R.H. Straub et al.

    Energy regulation and neuroendocrine-immune control in chronic inflammatory diseases

    J. Internal Med.

    (2010)
  • B.S. Nikolajczyk et al.

    The outliers become a stampede as immunometabolism reaches a tipping point

    Immunol. Rev.

    (2012)
  • K. Azim et al.

    Genetic polymorphisms and the risk of infection following esophagectomy. positive association with TNF-alpha gene -308 genotype

    Ann. Surg.

    (2007)
  • N. Kanbur et al.

    Tumor necrosis factor alpha-308 gene polymorphism in patients with anorexia nervosa

    Turk. J. Pediatr.

    (2008)
  • L. Di Renzo et al.

    Association between −308 G/A TNF-α polymorphism and appendicular skeletal muscle mass index as a marker of sarcopenia in normal weight obese syndrome

    Dis. Markers

    (2013)
  • Z. Yu et al.

    Genetic polymorphisms in adipokine genes and the risk of obesity: a systematic review and meta-analysis

    Obesity (Silver Spring)

    (2012)
  • M.S. Corbalán et al.

    Influence of two polymorphisms of the tumoral necrosis factor-alpha gene on the obesity phenotype

    Diabetes Nutr. Metab.

    (2004)
  • R. Aller et al.

    G308A polymorphism of TNF-alpha gene is associated with insulin resistance and histological changes in non alcoholic fatty liver disease patients

    Ann. Hepatol.

    (2010)
  • G. Morabito, C. Miglio, I. Peluso, M. Serafini, Chapter 85 – fruit polyphenols and postprandial inflammatory stress,...
  • I. Wybrańska et al.

    The TNF-alpha gene NcoI polymorphism at position −308 of the promoter influences insulin resistance, and increases serum triglycerides after postprandial lipaemia in familiar obesity

    Clin. Chem. Lab. Med.

    (2003)
  • A. Jatoi et al.

    A placebo-controlled double blind trial of etanercept for the cancer anorexia/weight loss syndrome: results from N00C1 from the North Central Cancer Treatment Group

    Cancer

    (2007)
  • I. Peluso et al.

    Flavonoids and immune function in human: a systematic review

    Crit. Rev. Food Sci. Nutr.

    (2015)
  • I. Peluso et al.

    Effect of flavonoids on circulating levels of TNF-α and IL-6 in humans: a systematic review and meta-analysis

    Mol. Nutr. Food Res.

    (2013)
  • I. Peluso et al.

    Interference of flavonoids with fluorescent intracellular probes: methodological implications in the evaluation of the oxidative burst by flow cytometry

    Cytometry A

    (2014)
  • K.M. Flegal et al.

    Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis

    JAMA

    (2013)
  • P. Wacharasint et al.

    One size does not fit all in severe infection: obesity alters outcome, susceptibility, treatment, and inflammatory response

    Crit. Care

    (2013)
  • I. Peluso et al.

    Interactions between prebiotics, probiotics, polyunsaturated fatty acids and polyphenols: diet or supplementation for metabolic syndrome prevention?

    Int. J. Food Sci. Nutr.

    (2014)
  • C.P. Chung et al.

    Inflammation-associated insulin resistance: differential effects in rheumatoid arthritis and systemic lupus erythematosus define potential mechanisms

    Arthritis Rheumatol.

    (2008)
  • L. Macia et al.

    Microbial influences on epithelial integrity and immune function as a basis for inflammatory diseases

    Immunol. Rev.

    (2012)
  • T. Karrasch et al.

    Systemic metabolic signaling in acute and chronic gastrointestinal inflammation of inflammatory bowel diseases

    Hormone Metab. Res.

    (2014)
  • A.L. Kau et al.

    Human nutrition, the gut microbiome and the immune system

    Nature

    (2011)
  • L. Mody et al.

    Urinary tract infections in older women: a clinical review

    JAMA

    (2014)
  • I. Peluso et al.

    Oxidative stress in atherosclerosis development: the central role of LDL and oxidative burst

    Endocrine Metab. Immune Disorders Drug Targets

    (2012)
  • C. Popa et al.

    Circulating leptin and adiponectin concentrations during tumor necrosis factor blockade in patients with active rheumatoid arthritis

    J. Rheumatol.

    (2009)
  • M.K. Badman et al.

    The gut and energy balance: visceral allies in the obesity wars

    Science

    (2005)
  • A.R. Johnson et al.

    The inflammation highway: metabolism accelerates inflammatory traffic in obesity

    Immunol. Rev.

    (2012)
  • P. Marques-Vidal et al.

    The association between inflammatory biomarkers and metabolically healthy obesity depends of the definition used

    Eur. J. Clin. Nutr.

    (2012)
  • C.M. Phillips et al.

    Does inflammation determine metabolic health status in obese and nonobese adults?

    J. Clin. Endocrinol. Metab.

    (2013)
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