Toll-like receptor 3 ablation prevented high-fat diet-induced obesity and metabolic disorder.

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.

• Authors: Guoqing Zhang, Ran Li, Wu Li, Sijia Yang, Qing Sun, Hongping Yin, Cui Wang, Biyu Hou, Huanhuan Wang, Liping Yu, Rucheng Chen, Liyun Shi, Kezhong Zhang, Chong Wee Liew, Guifen Qiang, Qinghua Sun, Cuiqing Liu
• Journal: The Journal of nutritional biochemistry (J Nutr Biochem) Vol. 95 Pg. 108761 (09 2021) ISSN: 1873-4847 [Electronic] United States
• PMID: 33965533 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021. Published by Elsevier Inc.

Chemical References

• TLR3 protein, human
• TLR3 protein, mouse
• Toll-Like Receptor 3

Topics

• Adult
• Animals
• Diet, High-Fat
• Female
• Gene Expression Regulation (physiology)
• Glucose Intolerance
• Glucose Metabolism Disorders
• Humans
• Intra-Abdominal Fat (metabolism)
• Lipid Metabolism
• Liver (metabolism)
• Macrophages (physiology)
• Male
• Metabolic Syndrome
• Mice
• Mice, Knockout
• Non-alcoholic Fatty Liver Disease
• Obesity
• Toll-Like Receptor 3 (genetics, metabolism)