Open AccessKnockdown of Tlr4 in the Arcuate Nucleus Improves Obesity Related Metabolic Disorders
Author(s) -
Yongli Zhao,
Guohua Li,
Ying Li,
Yuchuan Wang,
Zhengjuan Liu
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-07858-6
Subject(s) - gene knockdown , endocrinology , medicine , obesity , tlr4 , insulin resistance , inflammation , arc (geometry) , arcuate nucleus , energy homeostasis , diabetes mellitus , biology , hypothalamus , apoptosis , biochemistry , geometry , mathematics
High-fat diet-induced hypothalamic metabolic inflammation is emerging as a cause for the development of obesity. It is acknowledged that Toll-like receptor4 (TLR4) signaling plays a crucial role in triggering of the hypothalamic metabolic inflammation during the course of diet-induced obesity. Whether hypothalamic arcuate nucleus (ARC)-restricted TLR4 knockdown improves obesity-related metabolic disorders remains unexplored. In this study, we used TLR4 shRNA lentiviral particles to suppress the TLR4 expression in the hypothalamic ARC of diet-induced obese rat model by stereotaxic injection. Our results demonstrate that ARC-restricted TLR4 knockdown protects obese rats from diet-induced weight gain and energy intake, from diet-induced impaired glucose homeostasis and peripheral insulin resistance, and from high-fat diet-induced hepatic steatosis and adipocyte hypertrophy. Thus, we define ARC-restricted TLR4 knockdown as a potential strategy to combat metabolic disorders associated with obesity.