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      Juvenile Obesity Aggravates Disease Severity in a Rat Model of Atopic Dermatitis

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          Abstract

          Purpose

          There is increasing epidemiological evidence of an association between childhood obesity and atopic dermatitis, but little is known about the underlying mechanism(s). In the present study, we used a rat model of atopic dermatitis to assess whether juvenile obesity, induced by reduction of litter size, aggravated the signs of atopic dermatitis and, if so, whether this aggravation was associated with changes in plasma concentration of adipokines, such as leptin and adiponectin.

          Methods

          Dermatitis was induced by neonatal capsaicin treatment. Body weight, dermatitis score, serum IgE, skin nerve growth factor (NGF), serum leptin and adiponectin, and cytokine mRNA expression in the skin lesion were compared between small (SL, 5 pups) and large litters (LL, 15 pups).

          Results

          The body weight of juvenile rats up to 6 weeks of age was significantly heavier in the SL group, compared with those in the LL group. The SL group showed more robust development of dermatitis, and higher levels of serum IgE and skin NGF than the LL group. Additionally, the SL group demonstrated higher levels of leptin and pro-inflammatory cytokine mRNA but lower levels of adiponectin than the LL group.

          Conclusions

          These results suggest a causal link between a decrease in immunological tolerance, induced by juvenile obesity, and aggravation of atopic dermatitis.

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          Most cited references31

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          Adipose tissue, adipokines, and inflammation.

          White adipose tissue is no longer considered an inert tissue mainly devoted to energy storage but is emerging as an active participant in regulating physiologic and pathologic processes, including immunity and inflammation. Macrophages are components of adipose tissue and actively participate in its activities. Furthermore, cross-talk between lymphocytes and adipocytes can lead to immune regulation. Adipose tissue produces and releases a variety of proinflammatory and anti-inflammatory factors, including the adipokines leptin, adiponectin, resistin, and visfatin, as well as cytokines and chemokines, such as TNF-alpha, IL-6, monocyte chemoattractant protein 1, and others. Proinflammatory molecules produced by adipose tissue have been implicated as active participants in the development of insulin resistance and the increased risk of cardiovascular disease associated with obesity. In contrast, reduced leptin levels might predispose to increased susceptibility to infection caused by reduced T-cell responses in malnourished individuals. Altered adipokine levels have been observed in a variety of inflammatory conditions, although their pathogenic role has not been completely clarified.
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            Worldwide trends in childhood overweight and obesity.

            Obesity has become a global epidemic but our understanding of the problem in children is limited due to lack of comparable representative data from different countries, and varying criteria for defining obesity. This paper summarises the available information on recent trends in child overweight and obesity prevalence. PubMed was searched for data relating to trends over time, in papers published between January 1980 and October 2005. Additional studies identified by citations in retrieved papers and by consultation with experts were included. Data for trends over time were found for school-age populations in 25 countries and for pre-school populations in 42 countries. Using these reports, and data collected for the World Health Organization's Burden of Disease Program, we estimated the global prevalence of overweight and obesity among school-age children for 2006 and likely prevalence levels for 2010. The prevalence of childhood overweight has increased in almost all countries for which data are available. Exceptions are found among school-age children in Russia and to some extent Poland during the 1990s. Exceptions are also found among infant and pre-school children in some lower-income countries. Obesity and overweight has increased more dramatically in economically developed countries and in urbanized populations. There is a growing global childhood obesity epidemic, with a large variation in secular trends across countries. Effective programs and policies are needed at global, regional and national levels to limit the problem among children.
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              Reciprocal association of C-reactive protein with adiponectin in blood stream and adipose tissue.

              High-sensitive C-reactive protein (hs-CRP) is a well-known risk factor for coronary artery disease (CAD). Recently, we have demonstrated that adiponectin served as an antiatherogenic plasma protein which was secreted specifically from adipocytes. The present study investigated the association between adiponectin and CRP in the blood stream and adipose tissue. We studied a total of 101 male patients, 71 of whom had angiographically documented coronary atherosclerosis. As a control group, 30 patients with normal coronary angiogram were included. The plasma hs-CRP levels were negatively correlated with the plasma adiponectin levels (r=-0.29, P<0.01). The plasma adiponectin concentrations were significantly lower and the hs-CRP levels were significantly higher in the CAD patients compared with control subjects. The mRNA levels of CRP and adiponectin were analyzed by quantitative real-time polymerase chain reaction method. We found that the CRP mRNA was expressed in human adipose tissue. A significant inverse correlation was observed between the CRP and adiponectin mRNA levels in human adipose tissue (r=-0.89, P<0.01). In addition, the CRP mRNA level of white adipose tissue in adiponectin deficient mice was higher than that of wild-type mice. The reciprocal association of adiponectin and CRP levels in both human plasma and adipose tissue might participate in the development of atherosclerosis.
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                Author and article information

                Journal
                Allergy Asthma Immunol Res
                Allergy Asthma Immunol Res
                AAIR
                Allergy, Asthma & Immunology Research
                The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Disease
                2092-7355
                2092-7363
                January 2015
                09 July 2014
                : 7
                : 1
                : 69-75
                Affiliations
                Neuroscience Research Institute & Department of Physiology, Korea University College of Medicine, Seoul, Korea.
                Author notes
                Correspondence to: Heung Sik Na, MD, PhD, Department of Physiology, Korea University College of Medicine, 73 Inchon-ro, Seongbuk-gu, Seoul 136-705, Korea. Tel: +82-2-2286-1188; Fax: +82-2-925-5492; hsna@ 123456korea.ac.kr
                Correspondence to: Seung Keun Back, PhD, Department of Physiology, Korea University College of Medicine, 73 Inchon-ro, Seongbuk-gu, Seoul 136-705, Korea. Tel: +82-2-2286-1202; Fax: +82-2-925-5492; skback@ 123456korea.ac.kr
                Article
                10.4168/aair.2015.7.1.69
                4274472
                25553265
                45f4df09-a5f1-4bd7-9158-e8d241718506
                Copyright © 2015 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 03 December 2013
                : 31 March 2014
                : 16 April 2014
                Funding
                Funded by: National Research Foundation of Korea
                Award ID: NRF-2012-0009675
                Award ID: NRF-2013R1A1A2011913
                Funded by: Korea University
                Categories
                Original Article

                Immunology
                atopic dermatitis,juvenile obesity,adipokine,leptin,adiponectin,breast-feeding
                Immunology
                atopic dermatitis, juvenile obesity, adipokine, leptin, adiponectin, breast-feeding

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