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<div about="/news-events/nih-research-matters/obesity-alters-response-anti-inflammatory-treatment" typeof="sioc:Item foaf:Document" class="ds-1col node node--nih-research-matters view-mode-full node--full node--nih-research-matters--full clearfix">
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<p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2022-04-26T00:00:00-04:00" class="date-display-single">April 26, 2022</span></p><div class='syndicate'><h1>Obesity alters response to anti-inflammatory treatment</h1><div class="callout callout-with-border"><h3>At a Glance</h3>
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<ul>
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<li>A treatment for severe skin inflammation that works well in lean mice made the condition worse in obese mice because of immune-cell changes associated with obesity.</li>
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<li>The results highlight how obesity can alter the immune response, and how treatments for inflammatory conditions may need to account for body weight.</li>
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</ul></div><div class="media-float-right"><div class="ds-1col file file-image file-image-jpeg view-mode-floated_media clearfix">
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<picture title="Dermatologist wearing gloves examines the skin of a patient with eczema">
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-large/public/news-events/research-matters/2022/20220426-inflamitory-1.jpg?itok=V3YoKZI8&timestamp=1650916321 1x" media="screen and (min-width: 960px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2022/20220426-inflamitory-1.jpg?itok=G1KbWddI&timestamp=1650916321 1x" media="screen and (min-width: 800px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium-small/public/news-events/research-matters/2022/20220426-inflamitory-1.jpg?itok=VOifhShX&timestamp=1650916321 1x" media="screen and (min-width: 600px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-small/public/news-events/research-matters/2022/20220426-inflamitory-1.jpg?itok=yDjFmBWU&timestamp=1650916321 1x" media="screen and (min-width: 480px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-tiny/public/news-events/research-matters/2022/20220426-inflamitory-1.jpg?itok=6lyMYATr&timestamp=1650916321 1x" media="screen and (min-width: 0)" />
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<!--[if IE 9]></video><![endif]-->
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<img src="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2022/20220426-inflamitory-1.jpg?itok=G1KbWddI&timestamp=1650916321" alt="Dermatologist wearing gloves examines the skin of a patient with eczema" title="Dermatologist wearing gloves examines the skin of a patient with eczema" />
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</picture><span class="caption">The results suggest that treatments for skin conditions like eczema can be affected by body weight. </span><span class="credit">Fuss Sergey / Shutterstock</span></div>
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</div><p>Obesity is a growing health problem worldwide. Studies estimate that, by the year 2030, more than half of adults in the U.S. will be obese. Excess weight is associated with an increased risk of many health conditions. It’s also thought to impact the immune system. But the mechanisms in the body that lead to these effects aren’t fully understood.</p>
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<p>A team led by researchers from the Gladstone Institutes, the Salk Institute, and the University of California, San Francisco, has been studying these mechanisms and how they relate to inflammatory diseases, which involve problems with the immune system. In their new study, they examined differences in the immune response between obese and lean mice with atopic dermatitis, an itchy skin condition also known as eczema.</p>
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<p>The work was funded in part by several NIH components, including the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), and National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). Results were published on March 30, 2022, in <em>Nature</em>.</p>
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||
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||
<p>The team first tracked the development of eczema in obese and lean mice. They found that obese mice developed more inflammation and more severe eczema. This increased inflammation occurred even after obese mice lost weight. Similar results were seen in an experimental model of asthma, with obese mice developing more inflammation.</p>
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||
<p>The researchers next looked in detail at immune cells called T cells in lean and obese mice with eczema. Lean mice had more T<sub>H</sub>2 cells, a class of T cells known to play a role in the development of eczema. Obese mice had more of a class of T cells called T<sub>H</sub>17. These cells trigger a different type of inflammation.</p>
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||
|
||
<p>Similar trends were seen in blood samples taken from people. Markers of T<sub>H</sub>17 cell activity increased along with body mass index (BMI) in a database of serum collected from people with eczema. Conversely, in samples from patients with severe asthma, T<sub>H</sub>2 cell activity decreased as BMI increased.</p>
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||
<p>Drugs that block T<sub>H</sub>2 cell activity are used in the treatment of severe eczema as well as asthma and other inflammatory conditions. The researchers tested antibodies to block T<sub>H</sub>2 cell activity in lean and obese mice with severe eczema. While the antibodies reduced skin inflammation in lean mice as expected, they made the condition worse in obese mice. Analysis of immune cells suggested that blocking T<sub>H</sub>2 cell activity in the obese mice worsened other forms of inflammation.</p>
|
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<p>Further study found that obese mice appear to have less activity of a protein called PPARɣ in their T<sub>H</sub>2 cells. When the researchers engineered lean mice to lack PPARɣ, their inflammatory response resembled that of obese mice.</p>
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||
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||
<p>Drugs that increase PPARɣ activity increase insulin sensitivity and are approved for the treatment of type 2 diabetes. The researchers found that giving one of these drugs to obese mice changed their inflammatory response to resemble that of lean mice. It also restored their sensitivity to the antibodies that block T<sub>H</sub>2 cell activity.</p>
|
||
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||
<p>“Our findings demonstrate how differences in our individual metabolic states can have a major impact on inflammation, and how available drugs might be able to improve health outcomes,” says Dr. Ronald Evans from the Salk Institute, who helped lead the work.</p>
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<p>—by Sharon Reynolds</p></div><h2 class="label-above">Related Links</h2><ul class="spaced print-urls"><li><a href="https://www.nih.gov/news-events/nih-research-matters/repurposed-drug-combats-obesity-mice" target="_top">Repurposed Drug Combats Obesity in Mice</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/artificial-light-during-sleep-linked-obesity" target="_top">Artificial Light During Sleep Linked to Obesity</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/new-activity-anti-inflammatory-drugs" target="_top">New Activity for Anti-Inflammatory Drugs</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/benefits-moderate-weight-loss-people-obesity" target="_top">Benefits of Moderate Weight Loss in People with Obesity</a></li><li><a href="https://www.nhlbi.nih.gov/health/overweight-and-obesity" target="_top">Overweight and Obesity</a></li><li><a href="https://www.niaid.nih.gov/diseases-conditions/eczema-atopic-dermatitis" target="_top">Eczema (Atopic Dermatitis)</a></li><li><a href="https://www.cancer.gov/about-cancer/causes-prevention/risk/chronic-inflammation" target="_top">Chronic Inflammation</a></li></ul><p class="footnote"><strong class="label-inline">References: </strong><a href="https://pubmed.ncbi.nlm.nih.gov/35355021/">Obesity alters pathology and treatment response in inflammatory disease.</a> Bapat SP, Whitty C, Mowery CT, Liang Y, Yoo A, Jiang Z, Peters MC, Zhang LJ, Vogel I, Zhou C, Nguyen VQ, Li Z, Chang C, Zhu WS, Hastie AT, He H, Ren X, Qiu W, Gayer SG, Liu C, Choi EJ, Fassett M, Cohen JN, Sturgill JL, Crotty Alexander LE, Suh JM, Liddle C, Atkins AR, Yu RT, Downes M, Liu S, Nikolajczyk BS, Lee IK, Guttman-Yassky E, Ansel KM, Woodruff PG, Fahy JV, Sheppard D, Gallo RL, Ye CJ, Evans RM, Zheng Y, Marson A. <em>Nature</em>. 2022 Apr;604(7905):337-342. doi: 10.1038/s41586-022-04536-0. Epub 2022 Mar 30. PMID: 35355021.</p><p class="footnote"><strong class="label-inline">Funding: </strong>NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Heart, Lung, and Blood Institute (NHLBI), National Institute of General Medical Sciences (NIGMS), National Cancer Institute (NCI), National Institute of Environmental Health Sciences (NIEHS), and Office of the Director (OD); Korea Advanced Institute of Science and Technology; National Research Foundation of Korea; American Heart Association; United States Department of Veterans Affairs; March of Dimes; Samuel Waxman Cancer Research Foundation; NOMIS Foundation; Howard Hughes Medical Institute; Foundation Leducq, Don and Lorraine Freeberg Foundation; Larry L. Hillblom Foundation; David C. Copley Foundation; Crohn’s and Colitis Foundation; Leona M. and Harry B. Helmsley Charitable Trust; Burroughs Wellcome Fund; Chan Zuckerberg Biohub; Cancer Research Institute; Innovative Genomics Institute; Simons Foundation; Parker Institute for Cancer Immunotherapy; Byers Family; B. Bakar; K. Jordan; E. Radutzky; James B. Pendleton Charitable Trust.</p>
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