Combined exposure to lead and high-fat diet induced neuronal deficits in rats: Anti-neuroinflammatory role of SIRT1

Mengchen Liu; Rundong Liu; Mingzhi Yang; Yue Ba; Qihong Deng; Yu Zhang; Lin Han; Lihua Gao; Hui Huang

doi:10.1016/j.fct.2023.113857

Combined exposure to lead and high-fat diet induced neuronal deficits in rats: Anti-neuroinflammatory role of SIRT1

Food Chem Toxicol. 2023 Jul:177:113857. doi: 10.1016/j.fct.2023.113857. Epub 2023 May 26.

Authors

Mengchen Liu¹, Rundong Liu², Mingzhi Yang³, Yue Ba⁴, Qihong Deng⁵, Yu Zhang⁶, Lin Han⁷, Lihua Gao⁸, Hui Huang⁹

Affiliations

¹ Department of Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou, Henan province, 450001, China. Electronic address: [email protected].
² Department of Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou, Henan province, 450001, China. Electronic address: [email protected].
³ Department of Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou, Henan province, 450001, China. Electronic address: [email protected].
⁴ Department of Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou, Henan province, 450001, China. Electronic address: [email protected].
⁵ Department of Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou, Henan province, 450001, China. Electronic address: [email protected].
⁶ State Key Laboratory of Microbial Technology, Qingdao, Shandong, 266000, China; Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan, Shandong, 250100, China; Institute of Marine Science and Technology, Shandong University, Qingdao, Shandong, 266000, China. Electronic address: [email protected].
⁷ Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan, Shandong, 250100, China; Institute of Marine Science and Technology, Shandong University, Qingdao, Shandong, 266000, China. Electronic address: [email protected].
⁸ Zhengzhou Center for Disease Control and Prevention, Zhengzhou, Henan, 450052, China. Electronic address: [email protected].
⁹ Department of Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou, Henan province, 450001, China. Electronic address: [email protected].

PMID: 37244597
DOI: 10.1016/j.fct.2023.113857

Abstract

Introduction: Lead (Pb) exposure and high-fat diet (HFD) trigger neurotoxicity, which may involve neuroinflammation. However, the mechanism by which combined Pb and HFD exposure induces nucleotide oligomerization domain-like receptor family pyrin domain 3 (NLRP3) inflammasome activation has not been fully elucidated.

Material and methods: The Sprague-Dawley (SD) rat model of exposure to Pb and HFD was established to reveal the inﬂuence of co-exposure on cognition and identify signaling clues that mediate neuroinflammation and synaptic dysregulation. PC12 cells was treated with Pb and PA in vitro. Silent information regulator 1 (SIRT1) agonist (SRT 1720) was employed as intervention agent.

Results: Our results showed that Pb and HFD exposure induced cognitive impairment and lead to neurological damage in rats. Meanwhile, Pb and HFD could stimulate the NLRP3 inflammasome assembly and activate caspase 1, releasing proinflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18), further promoting neuronal cell activation and amplifying neuroinflammatory responses. Additionally, our findings suggest that SIRT1 plays a role in Pb and HFD induced neuroinflammation. However, the use of SRT 1720 agonists showed some potential in alleviating these impairments.

Conclusion: Pb exposure and HFD intake could induce neuronal damage through activation of the NLRP3 inflammasome pathway and synaptic dysregulation, while the NLRP3 inflammasome pathway may be rescued via activating SIRT1.

Keywords: High-fat diet; Lead; Neuroinflammation; SIRT1; Synaptic dysregulation.

MeSH terms

Animals
Diet, High-Fat / adverse effects
Heterocyclic Compounds, 4 or More Rings / pharmacology
Inflammasomes* / metabolism
Lead / toxicity
NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism
Neuroinflammatory Diseases
Rats
Rats, Sprague-Dawley
Sirtuin 1 / genetics

Substances

Inflammasomes
Lead
NLR Family, Pyrin Domain-Containing 3 Protein
Sirtuin 1
SRT1720
Heterocyclic Compounds, 4 or More Rings