{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T05:52:03Z","timestamp":1771307523903,"version":"3.50.1"},"reference-count":56,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T00:00:00Z","timestamp":1705881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013058","name":"Jiangsu Provincial Key Research and Development Program","doi-asserted-by":"publisher","award":["BE2021705"],"award-info":[{"award-number":["BE2021705"]}],"id":[{"id":"10.13039\/501100013058","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Innate immune receptor TLR4 plays an important role in glycolipid metabolism. The objective of this study is to investigate the inhibitory effects of blocking TLR4 on hyperglycemia and hyperlipidemia by comparing WT and TLR4\u2212\/\u2212 mice in obesity and diabetes modeling. The knockout of the TLR4 gene could prevent weight gain induced by a high-fat diet (HFD)\/high-sugar and high-fat diet (HSHFD), and the differences in the responses existed between the sexes. It extends the time required to reach the obesity criteria. However, when mice were injected with intraperitoneal streptozotocin (STZ) after being fed by HSHFD for two months, TLR4\u2212\/\u2212 mice exhibited less weight loss than WT. Blocking TLR4 alleviated the changes in body weight and blood glucose, consequently reducing the efficiency of diabetes modeling, especially for male mice. Additionally, male TLR4\u2212\/\u2212 obese mice exhibit lower total cholesterol (TC) and low-density lipoprotein (LDL) levels in serum and less formation of fat droplets in the liver compared to WT. On the other hand, the knockout of TLR4 significantly increased the high-density lipoprotein (HDL) of male mice. This study should provide new insights into the role of TLR4, as well as opportunities to target novel approaches to the prevention and treatment of metabolic diseases like obesity and diabetes.<\/jats:p>","DOI":"10.3390\/biology13010063","type":"journal-article","created":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T11:36:41Z","timestamp":1705923401000},"page":"63","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Inhibition of Hyperglycemia and Hyperlipidemia by Blocking Toll-like Receptor 4: Comparison of Wild-Type and Toll-like Receptor 4 Gene Knockout Mice on Obesity and Diabetes Modeling"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2596-5461","authenticated-orcid":false,"given":"Xingyu","family":"Zhao","sequence":"first","affiliation":[{"name":"Institute of Agro-Product Processing, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China"},{"name":"School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiawei","family":"Zheng","sequence":"additional","affiliation":[{"name":"School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Li","sequence":"additional","affiliation":[{"name":"College of Food Science, Shenyang Agricultural University, Shenyang 110866, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3038-0636","authenticated-orcid":false,"given":"Wuyang","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Agro-Product Processing, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China"},{"name":"School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China"},{"name":"College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1377\/hlthaff.2015.0371","article-title":"An integrated framework for the prevention and treatment of obesity and its related chronic diseases","volume":"34","author":"Dietz","year":"2015","journal-title":"Health Aff."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.diabres.2017.03.024","article-title":"IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040","volume":"128","author":"Ogurtsova","year":"2017","journal-title":"Diabetes Res. 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