Scientific Reports (Aug 2017)

Knockdown of Tlr4 in the Arcuate Nucleus Improves Obesity Related Metabolic Disorders

  • Yongli Zhao,
  • Guohua Li,
  • Ying Li,
  • Yuchuan Wang,
  • Zhengjuan Liu

DOI
https://doi.org/10.1038/s41598-017-07858-6
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 9

Abstract

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Abstract 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.