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Potential Mechanisms for Obesity-Asthma Link

M. Metin Donma1*
1Department of Pediatrics, Namik Kemal University, Medical Faculty, Tekirdag, Turkey

*Corresponding author:  Prof. M. Metin Donma in Pediatrics, Namik Kemal University, Medical Faculty, Tekirdag, Turkey, Tel: 90-282-2505631; Email: mdonma@gmail.com

Submitted04-30-2015 Accepted: 05-02-2015 Published: 05-07-2015

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Obesity and asthma prevalence have rapidly increased worldwide. Clinical and epidemiological studies support a strong positive relationship between these two chronic diseases, which are associated with inflammation. It is interesting to note that overweight and obese children are at higher risk for asthma. Obesity probably has an effect on asthma development through several different mechanisms [1,2].

Asthma and obesity are likely to be connected in a multifactorial fashion. Environmental and lifestyle changes (diet, physical activity, and early life exposures) as well as the presence of genetic susceptibilities are important, previously known factors contributing to the increase in their prevalence over the past few decades and have altered the occurrence and expression of asthma and obesity [1].

In recent years, there has been an accumulating body of evidence related to other possible mechanisms participating potentially in the link established between obesity and asthma. The biological mechanisms behind the link between body mass index (BMI) increase and asthma may be summarized in the following manner:

Anthropometric measurements are considered along with fat measurements for the evaluation of obese subjects. These parameters generally are not determined during the physical examination of asthmatic individuals. So far, waist circumference was found as the only measure that correlated with increased IgE levels and allergic rhinitis [3].

The mechanisms underlying the association between obesity and asthma severity may be related to a decreased immunological tolerance induced by a defective function of regulatory T cells (Tregs), which are responsible from the maintenance of peripheral tolerance [4-6]. Association between rapid weight gain in infancy and asthma or obesity development is suggested [6,7]. Tregs are the key players that prevent allergy development [8]. In a recently published article, significantly reduced Tregs were observed in obese, asthmatic and asthmatic obese children. Obesity and asthma are characterized by chronic and systemic inflammation, and reduction in Tregs may initiate inflammatory processes and cause obesity, which is higher in children with asthma [6].

Type of infant feeding has been matter of discussion for a long time. Effects of artificial formula feeding upon weight gain were pointed out years ago [9]. Pronounced early weight gain during infancy appears to be an important predictor for childhood asthma, particularly within the first 6 years of life [10]. Artificial formula feeding was introduced into infant nutrition before mammalian target of rapamycin (mTOR), cell’s master regulator of cell growth and proliferation, has been extensively studied. There is a direct link between amino acid availability and mTOR-driven cell growth [11].

Activation and generation of T cells are associated with the central role of mTOR activity [12]. Abundant amount of amino acids by excess protein intake due to artificial formula feeding within the postnatal period may lead to overstimulation of mTOR in many immune cells including T cells. High protein infant formula feeding overstimulating insulin finally activates mTOR [11,13]. mTOR signalling plays a role also during asthma. Inhibition of mTOR has been shown to alleviate cardinal asthmatic features, including airway hyperresponsiveness and eosinophilic inflammation. Increased mTOR signalling by high protein formula feeding may interfere with postnatal mTOR-mediated immune cell programming [11,14,15].

Increased expression of some proinflammatory cytokines such as tumor necrosis factor (TNF)-α has been introduced as a common factor in asthma and obesity and possibly an important target for obesity-related asthma in some experimental studies [16,17]. Restoring normal body weight has been suggested as an appropriate strategy for reducing TNF-α levels, and controlling inflammation, which may help improving asthma control in obesity-related asthma [16].

Adipocyte-derived parameters have recently gained importance. Besides proinflammatory parameters such as leptin, resistin and visfatin, adiponectin, with its antiinflammatory aspects, have recently contributed to the matter. Leptin is increased in obesity and leads to increased neutrophil recruitment to the lungs. Leptin signalling negatively modulates Tregs function. The increased asthma severity in obesity might be caused by decreased immunological tolerance induced by a decreased function of Tregs mediated by leptin [4]. Elevated leptin, resistin and visfatin levels accompanying diminished concentration of adiponectin have been reported in asthmatic obese children and systemic inflammatory biomarkers are found to be correlated with BMI values [18,19]. The leptin-adiponectin balance is disturbed in obese individuals and this may cause neutrophilic airway inflammation [20].

Adipokines can also affect the survival and function of eosinophils. Leptin has proinflammatory systemic activities that may contribute, at least in part, to asthma. Leptin activates eosinophils and thus may serve as an important eosinophil survival factor through anti-apoptotic activity. The links between eosinophilic activity and leptin suggest that leptin is involved in enhanced eosinophil accumulation into the airways of obese individuals [21].

Obesity is commonly associated with hypertriglyceridemia, hypercholesterolemia and insulin resistance. Since dyslipidemia and hyperinsulinemia are also involved in the development of airway inflammation, they may help to explain the link between obesity and asthma [1, 2,22]

Obesity in childhood is also a significant predictor of obesity in adulthood. Particularly, asthmatic obese children should be handled with utmost care because this is an expanding area on which studies must be focused.

Studies must be organized in both adult and pediatric population to observe the similarities and differences in terms of mechanisms. Due to changes, including hormones, associated with puberty, particularly alterations in insulin sensitivity, the adolescence period must be evaluated individually as prepubertal and postpubertal periods. Gender differences are also to be taken into account. Distribution of body fat must also be considered.

Studies on molecular and cellular medicine aspects of this topic must also be performed, because apoptosis, phagocytosis and efferocytosis are the processes, which are known to contribute to the establishment and progression of such chronic inflammatory diseases.

Wide-scoped, case-controlled, multi-centered and longitudinal studies considering nutritional aspects, adipotropins as well as hormones derived from adipocytes, proinflammatory cytokines, T cells, mTOR and also genetic and environmental factors are indispensable to solve this sophisticated problem and to clear this rather enigmatic relationship between these two diseases of the age. Advancement in understanding associations of obesity with asthma will allow advancement in developing more effective, straightforward and complete therapeutic solutions.



1.Rasmussen F, Hancox RJ. Mechanisms of obesity in asthma. In Curr Opin Allergy Clin Immunol. 2014, 14(1): 35-43.

2.Papoutsakis C, Priftis KN, Drakouli M, Prifti S, Konstantaki E et al. Childhood overweight/obesity and asthma: Is there a link? A systematic review of recent epidemiologic evidence. In J Acad Nutr Diet. 2013, 113(1): 77-105.

3.Arteaga-Solis E, Kattan M. Obesity in asthma: Location or hormonal consequences?. In J Allergy Clin Immunol. 2014, 133(5): 1315-1316.

4.Mascitelli L, Pezzetta F, Goldstein MR. Leptin and regulatory T cells in obese patients with asthma. In Thorax. 2008, 63:659.

5.Taylor B, Mannino D, Brown C, Crocker D, Twum-Baah N et al. Body mass index and asthma severity in the National Asthma Survey. In Thorax 2008, 63(1): 14-20.

6.Donma M, Karasu E, Ozdilek B, Turgut B, Topcu BE et al. CD4+, CD25+, FOXP3+ T regulatory cell levels in obese, asthmatic, asthmatic obese and healthy children. Inflammation, in press. 2015.

7.Mai XM, Gäddlin PO, Nilsson L, Leijon I. Early rapid weight gain and current overweight in relation to asthma in adolescents born with very low birth weight. In Pediatr Allergy Immunol 2005, 16(5): 380-385.

8.Palomares O, Yaman G, Azkur AK, Akkoc T, Akdis M, et al. Role of Treg in immune regulation of allergic diseases. In Eur J Immunol. 2010, 40(5): 1232-1240.

9.Donma MM, Donma O. Infant feeding and growth. A study on Turkish infants from birth to 6 months. In Pediatr Int. 1999, 41(5): 542-548.

10.Brüske I, Flexeder C, Heinrich J. Body mass index and the incidence of asthma in children. In Curr Opin Allergy Clin Immunol. 2014, 14(2): 155-160.

11.Melnik BC. The potential mechanistic link between allergy and obesity development and infant formula feeding. In Allergy Asthma Clin Immunol. 2014, 10(1): 37.

12.Powell JD, Delgoffe GM. The mammalian target of rapamycin: linking T cell differentiation, function and metabolism. In Immunity. 2010, 33(3): 301-311.

13.Schwarz JJ, Wiese H, Toelle RC, Zarei M, Dengjel J et al. Functional proteomics identifies acinus L as a direct insulin- and amino acid-dependent mTORC1 substrate. Mol Cell Proteomics, in press. 2015, 14(5).

14.Mushaben EM, Kramer EL, Brandt EB, Khurana Hershey GK, Le Cras TD. Rapamycin attenuates airway hyperreactivity, goblet cells, and IgE in experimental allergic asthma. In J Immunol. 2011, 187(11): 5756-5763.

15.Choi YH, Jin GY, Li LC, Yan GH. Inhibition of protein kinase C delta attenuates allergic airway inflammation through suppression of PI3K/Akt/mTOR/HIF-1 alpha/VEGF pathway. In PLoS ONE. 2013, 8(11): e81773.

16.Kim JY, Sohn JH, Lee JH, Park JW. Obesity increases airway hyperresponsiveness via the TNF-α pathway and treating obesity induces recovery. In PLoS ONE 2015, 10(2): e116540.

17.Calixto MC, Lintomen L, Andre DM, Leiria LO, Ferreira D et al. Metformin attenuates the exacerbation of the allergic eosinophilic inflammation in high fat-diet-induced obesity in mice. In PLoS ONE 2013, 8(10): e76786.

18.Magrone T, Simone M, Altamura M, Munno I. Characterization of the immune inflammatory profile in obese asthmatic children. In Endocr Metab Immune Disord Drug Targets. 2014, 14(3): 187-195.

19.Rojas-Dotor S, Segura-Méndez NH, Mijagui-Namikawa K, Mondragón-González R. Expression of resistin CXCR3, IP- 10, CCR5 and MIP-1α in obese patients with different severity of asthma. In Biol Res. 2013, 46(1): 13-20.

20.Gibson PG. Obesity and asthma. In AnnalsATS. 2013, 10: S138-S142.

21.Kim SH, Sutherland ER, Gelfand EW. Is there a link between obesity and asthma. In Allergy Asthma

22.Immunol Res. 2014, 6(3): 189-195.

23.Shore SA. Obesity and asthma: Possible mechanisms. In J Allergy Clin Immunol. 2008, 121(5): 1085-1094.

Cite this article: Donma MM. Potential Mechanisms for Obesity-Asthma Link . J J Obesity. 2015, 1(1): 003.



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