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It has become evident over the last decades that a low-grade inflammatory response, primarily proceeding from the adipose tissue (AT), essentially contributes to adiposity-associated comorbidities, most prominently insulin resistance (IR), atherosclerosis and liver diseases. In mouse models, the release of pro-inflammatory cytokines such as TNF-alpha (TNF-\u03b1) and interleukin (IL)-1\u03b2 and the imprinting of immune cells to a pro-inflammatory phenotype in AT play an important role. However, the underlying genetic and molecular determinants are not yet understood in detail. Recent evidence demonstrates that nucleotide-binding and oligomerization domain (NOD)-like receptor (NLR) family proteins, a group of cytosolic pattern recognition receptors (PRR), contribute to the development and control of obesity and obesity-associated inflammatory responses. In this article, we review the current state of research on the role of NLR proteins in obesity and discuss the possible mechanisms leading to and the outcomes of NLR activation in the obesity-associated morbidities IR, type 2 diabetes mellitus (T2DM), atherosclerosis and non-alcoholic fatty liver disease (NAFLD) and discuss emerging ideas about possibilities for NLR-based therapeutic interventions of metabolic diseases.<\/jats:p>","DOI":"10.3390\/ijms24108595","type":"journal-article","created":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T04:29:01Z","timestamp":1683779341000},"page":"8595","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["NOD-like Receptors\u2014Emerging Links to Obesity and Associated Morbidities"],"prefix":"10.3390","volume":"24","author":[{"given":"Sarah","family":"Bauer","sequence":"first","affiliation":[{"name":"Institute of Nutritional Medicine, Department of Immunology, University of Hohenheim, 70593 Stuttgart, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2670-6365","authenticated-orcid":false,"given":"Lucy","family":"Hezinger","sequence":"additional","affiliation":[{"name":"Institute of Nutritional Medicine, Department of Immunology, University of Hohenheim, 70593 Stuttgart, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fjolla","family":"Rexhepi","sequence":"additional","affiliation":[{"name":"Department of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheela","family":"Ramanathan","sequence":"additional","affiliation":[{"name":"Department of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4563-0412","authenticated-orcid":false,"given":"Thomas A.","family":"Kufer","sequence":"additional","affiliation":[{"name":"Institute of Nutritional Medicine, Department of Immunology, University of Hohenheim, 70593 Stuttgart, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/S0140-6736(14)60460-8","article-title":"Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: A systematic analysis for the Global Burden of Disease Study 2013","volume":"384","author":"Ng","year":"2014","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1016\/S0140-6736(05)66378-7","article-title":"The metabolic syndrome","volume":"365","author":"Eckel","year":"2005","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/nature05485","article-title":"Inflammation and metabolic disorders","volume":"444","author":"Hotamisligil","year":"2006","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1146\/annurev-physiol-021909-135846","article-title":"Macrophages, inflammation, and insulin resistance","volume":"72","author":"Olefsky","year":"2010","journal-title":"Annu. 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