Toll-like receptor 3 ablation prevented high-fat diet-induced obesity and metabolic disorder |
| |
| Affiliation: | 1. School of Public Health and Joint China-US Research Center for Environment and Pulmonary Diseases, Zhejiang Chinese Medical University, Hangzhou, China;2. College of Medicine, Hangzhou Normal University, Hangzhou, China;3. Department of Gynecology, Tongde Hospital of Zhejiang Province, Hangzhou, China;4. College of Life Science, Zhejiang Chinese Medical University, Hangzhou, China;5. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China;6. Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan, USA;7. Department of Physiology & Biophysics, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA;8. College of Public Health, The Ohio State University, Columbus, Ohio, USA;1. Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China;2. Medical Research Center, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China;3. School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang 311399, China;4. Affiliated Xiangshan Hospital of Wenzhou Medial University (Xiangshan First People''s Hospital Medical and Health Group), Xiangshan, Zhejiang 315799, China;1. Grup de Recerca Nutrigenòmica i Obesitat, Laboratori de Biologia Molecular, Nutrició i Biotecnologia (LBNB), Universitat de les Illes Balears, Palma de Mallorca, Spain;2. Institut d''Investigació Sanitària Illes Balears (IdISBa), Palma de Mallorca, Spain;3. CIBER de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Palma de Mallorca, Spain;1. Department of Internal Medicine, University of Manitoba, Winnipeg, Canada;2. Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada;3. School of Public Health, Sun Yat-sen University, Guangzhou, China |
| |
| Abstract: | Inflammation in insulin-sensitive tissues (e.g., liver, visceral adipose tissue [VAT]) plays a major role in obesity and insulin resistance. Recruitment of innate immune cells drives the dysregulation of glucose and lipid metabolism. We aimed to seek the role of Toll like receptor 3 (TLR3), a pattern recognition receptor involved in innate immunity, obesity and the metabolic disorder. TLR3 expression in liver and VAT from diet induced obese mice and in VAT from overweight women was examined. Body weight, glucose homeostasis and insulin sensitivity were evaluated in TLR3 wild-type and knockout (KO) mice on a chow diet (CD) or high-fat diet for 15 weeks. At euthanasia, blood was collected, and plasma biochemical parameters and adipokines were determined with commercial kits. Flow cytometry was used to measure macrophage infiltration and activation in VAT. Standard western blot, immunohistochemistry and quantative PCR were used to assess molecules in pathways about lipid and glucose metabolism, insulin and inflammation in tissues of liver and VAT. Utilizing human and animal samples, we found that expression of TLR3 was upregulated in the liver and VAT in obese mice as well as VAT in overweight women. TLR3-deficiency protected against high-fat diet induced obesity, glucose intolerance, insulin resistance and lipid accumulation. Lipolysis was enhanced in VAT and hepatic lipogenesis was inhibited in TLR3 KO animals. Macrophages infiltration into adipose tissue was attenuated in TLR3 KO mice, accompanied with inhibition of NF-κB-dependent AMPK/Akt signaling pathway. These findings demonstrated that TLR3 ablation prevented obesity and metabolic disorders, thereby providing new mechanistic links between inflammation and obesity and associated metabolic abnormalities in lipid/glucose metabolism. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
