ReviewThe relationship between body weight and inflammation: Lesson from anti-TNF-α antibody therapy
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.
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